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Breast Cancer Overview - Signaling Pathway. Diagnostics Marker. Targeted Therapy and Clinical Trials.

Breast Cancer Signaling Pathway

Fig.1 Breast cancer signaling pathway. Targeted agents (listed in orange boxes) include those in clinical use (colored in green) and those in preclinical or early phase development (colored in red) for the treatment of advanced stage breast cancer.

An Introduction to Breast Cancer

Breast cancer (BC) is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland. As a heterogeneous disease, breast cancer encompasses a wide variety of pathological entities and this heterogeneity is reflected by the differences in cell type composition and proportions, the differences in the proliferation ability between glandular and myoepithelial cells, the proliferation of progenitor cells, the therapeutic responses and patient outcomes. The molecular subtypes of breast cancer, which are based on the presence or absence of hormone receptors (estrogen and progesterone subtypes) and human epidermal growth factor receptor-2 (HER2), include: hormone receptor positive and HER2 negative (luminal A subtype), hormone receptor positive and HER2 positive (luminal B subtype), hormone receptor negative and HER2 positive (HER2 positive), and hormone receptor negative and HER2 negative (basal-like or triple-negative breast cancers (TNBCs)). Hormone receptor positive breast cancers are largely driven by the estrogen/ER pathway. In HER2 positive breast tumours, HER2 activates the PI3K/AKT and the RAS/RAF/MAPK pathways, and stimulate cell growth, survival and differentiation. In patients suffering from TNBC, the deregulation of various signalling pathways (Notch and Wnt/beta-catenin), EGFR protein have been confirmed.

1 Main Signaling Pathways in Breast Cancer Therapy

1.1 RTK signaling cascade

The activation of the RTK cascade is mostly initiated at membrane receptors, such as HER2, EGFR, IGFR, FGFR1, KIT. The binding of receptors and ligands activate the phosphatidylinositol-3-kinase (PI3K) or Ras signaling pathway. When PI3K is activated, it phosphorylates inositol-containing membrane lipids. The phosphorylation product PIP3 binds to AKT. In addition, PTEN have no activity to inhibit Akt activity by dephosphorylation of PIP3 in breast cancer cells. AKT then phosphorylates several substrates, leading to the activation of the so-called mammalian target of rapamycin (mTOR). When Ras pathway is activated, Ras proteins transduce signals from extracellular growth factors by cycling between inactive GDP-bound and active GTP-bound states and turn on the downstream RAF protein kinases. The dominant substrates of RAF kinases are the MAPK/ERK kinases, MEK1 and MEK2. ERK generates extensive changes in gene expression mediated by transcription factors that control cell cycle progression, differentiation.

1.2 Notch signaling cascade

The activation of Notch cascade is mostly initiated at the binding of extracellular domain of Notch receptors (NICD) and ligands (Jagged, Delta). NICD translocates to the nucleus, causing transactivation of downstream target genes including several genes (Hes, Hey). These transcriptional targets include transcription factors (NF-κB2 and c-Myc), cell-cycle regulators (cyclin D1 and p21), and growth factor receptors (HER2) and regulators of angiogenesis and apoptosis. So the interruption of the Notch pathway can thus have noteworthy downstream effects on differentiation, angiogenesis and apoptosis, cell growth.

1.3 Wnt signaling cascade

The Wnt pathway is activated by the up regulated Wnt receptor frizzled-7 (FZD7) and the Wnt co-receptor LRP6. Signaling via Dishevelled and/or Axin then results in inactivation of a multiprotein complex that normally renders β-catenin unstable. Once in the nucleus, β-catenin binds to proteins of the T-cell factor (TCF)/lymphoid enhancer factor-1 (LEF1) family and modulates the expression of several target genes. Several Wnt/β-catenin target genes have been identified, including those that control cell proliferation and apoptosis, thus mediating cancer initiation and progression.

1.4 Estrogen signaling cascade

The Estrogen pathway of breast cancer through ‘nuclear-initiated steroid signaling’ mediates its cellular actions. The cytoplasmic estrogens bind directly to the nuclear membrane estrogen receptor which in turn translocates to the nucleus, binds DNA at ERE elements and activates the expression of ERE-dependent genes. These ERE-dependent genes appears to regulate a set of genes involved in the differentiation and proliferation of breast cancer cells.

2  Breast cancer diagnosis

2.1 Molecular Markers for Breast Cancer

Although the most of these markers is protein, gene expression patterns and altered DNA identified in tumor tissue have also taken prominence as tumor markers. It is known that breast cancer represents a complex and heterogeneous disease that comprises distinct pathologies, histological features, and clinical outcome. Also, it is well established that this neoplasia has well-defined molecular subgroups based on gene expression profiling closely related to the behavior of these molecular subtypes. Some researchers pointed out that results from studies of gene expression profiling have altered the view of breast cancer and provided a new tool for molecular diagnosis. Actually, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor type 2 (HER2) has been used as predictive markers for identifying a high-risk phenotype and for selection of the most efficient therapies. After the sequencing of human genome and the technical progress in protein identification, it is reasonable considering an integrated program of genomics and proteomics to accomplish better comprehension of breast cancer features and the development of improved therapeutics. Together, these results strengthened evidence of improved sensitivity and resolution methodologies,which contribute to the classification of breast cancer.

RNA and DNA can also be tested in routine paraffin-embedded tissue samples, and in situ hybridization can detect HER2 amplification as a confirmatory test for IHC or as a stand-alone assay. There is great interest in other actionable targets in cancer genomes for precision therapy using next-generation gene sequencing. DNA microarrays and high-throughput reverse transcription-polymerase chain reaction assays for multiple genes can be used to categorize breast cancers into several prognostic groups. Gene assays are used to predict the risk of distant recurrence in early-stage breast cancer and to infiuence decisions about systemic therapy. These tests rely heavily on the assessment of ER and proliferation-related genes, such as Ki-67, and have largely replaced the use of other, single markers of risk in clinical practice.

2.2 Protein Markers for Breast Cancer

Women with the so-called ‘triple negative’ subtype of breast cancer have poor prognosis and survival compared to other subtypes due to the aggressive nature of these tumours and the current absence of suitable targets for therapy.

The majority of breast tumours are ER, PR, or HER2+ positive and can be effectively treated with targeted therapies directed against these proteins, such as hormonal therapies blocking production or function of oestrogens, and antibody or kinase inhibitor therapies blocking the HER2 pathway. However, about 15 percent of breast tumours are triple negative and effective treatment is not readily available. Identification of protein markers that are specifically expressed in triple negative tumours would not only benefit proper clinical classification, but would provide the basis for development of new, targeted therapies against this aggressive type of breast cancer. Critical treatment decisions are made on the basis of protein expression assays that are independent of tumor morphologic characteristics. IHC analysis of paraffin sections is routinely performed for the evaluation of estrogen receptor (ER), progesterone receptor (PR), and Her-2/neu (HER2) status. Although widely used to predict responses to targeted agents, histologic tumor markers are limited by significant intratumoral variation, even within a single biopsy specimen.

3 Targeted therapy for breast cancer

The RTK /Notch/Wnt/Estrogen signaling pathway plays prominent roles in malignant transformation, prevention of apoptosis, drug resistance and metastasis. The expresaberrant expression of: HER2, ER, PR, BRCA1, BRCA2, EGFR1, PIP3, PTEN, P53, as well as other oncogenes and tumor suppressor genes. A greater understanding of the underlying biology of breast cancer has resulted in the identification of a number of molecular targets and development of  therapeutics intervention.

We have focused on recently discovered therapeutic targets for breast cancer, such as the RTK signaling pathway, Notch signaling pathway, Wnt/β-catenin pathway, Estrogen/ER signaling pathway, EGFR inhibitors, PARP1 inhibitors, and mammalian target of rapamycin (mTOR) inhibitors, as well as a few therapeutic options that have recently been developed for the treatment of breast cancer based on these targets along with their progress in clinical trials (Table 1-13).

3.1 Breast cancer therapy for BRCA1 and BRCA2 mutations

PARP1, a poly ADP-ribose polymerase, is a member of a family of enzymes that remove damaged and (or) incorrect DNA sequences by different excision repair pathways, involving base excision repair, nucleotide excision repair and mismatch repair by filling the ensuing gap using the complementary DNS strand as a template. Therefore, a cancer that involves a mutation in these BRAC1 and BRAC2 genes (BRCAness) can be effectively treated with PARP1 inhibitors such as Olaparib, Iniparib, which may represent very efficient therapies for breast cancer because of the high sensitivity of these tumours to the inhibitor and more importantly.

Table 1 Clinical trials of PARP1 inhibitor Olaparib

Nct id Status Lead sponsor Study first posted
NCT02032823 Recruiting AstraZeneca January 10, 2014
NCT03205761 Recruiting Spanish Breast Cancer Research Group July 2, 2017
NCT03150576 Recruiting Cambridge University Hospitals NHS Foundation Trust May 12, 2017
NCT03167619 Not yet recruiting Kimberly Blackwell May 30, 2017
NCT03594396 Recruiting Seoul National University Hospital July 20, 2018
NCT03367689 Recruiting MedSIR December 11, 2017
NCT01623349 Active, not recruiting Dana-Farber Cancer Institute June 20, 2012
NCT02227082 Recruiting The Netherlands Cancer Institute August 27, 2014
NCT03109080 Recruiting Institut Curie April 12, 2017
NCT02789332 Recruiting German Breast Group June 3, 2016
NCT03544125 Recruiting OHSU Knight Cancer Institute June 1, 2018
NCT02849496 Recruiting National Cancer Institute (NCI) July 29, 2016
NCT02208375 Active, not recruiting M.D. Anderson Cancer Center August 5, 2014
NCT02299999 Recruiting UNICANCER November 24, 2014
NCT02684318 Recruiting Poveda, Andrés, M.D. February 18, 2016
NCT01042379 Recruiting QuantumLeap Healthcare Collaborative January 5, 2010
NCT02624973 Recruiting Haukeland University Hospital December 9, 2015

According to statistics, a total of 17 Olaparib projects targeting breast cancer BRCAness are currently in clinical stage, of which 14 are recruiting and 3 are not recruiting.

3.2 Breast cancer therapy for RTK pathway

The RTK pathway generates Akt (PKB) and MAPK causing drug resistance. In addition, it regulates cell proliferation, differentiation, invasion, angiogenesis and apoptosis through various signaling pathways and serves as a poor prognostic factor in cancer, and the RTK pathway could be a therapeutic target for women with BC that effectively treated with HER2 inhibitors Herceptin, Lapatinib, EGFP inhibitors Gefitinib, Cetuximab, KIT inhibitors Sorafenib, mTOR inhibitors Everolumus, Temsirolimus, Cisplatin, Erlotinib.

Table 2 Clinical trials of HER-2 mAB Herceptin

Nct id Status Lead sponsor Study first posted
NCT01325207 Active, not recruiting Northwestern University March 29, 2011
NCT00470704 Active, not recruiting Nancy Lin, MD May 8, 2007
NCT00004935 Active, not recruiting Swiss Group for Clinical Cancer Research January 27, 2003
NCT02297698 Recruiting Cancer Insight, LLC November 21, 2014
NCT00428922 Active, not recruiting Bhuvaneswari Ramaswamy January 30, 2007
NCT03085368 Recruiting Peking Union Medical College Hospital March 21, 2017
NCT03433313 Not yet recruiting EirGenix, Inc. February 14, 2018
NCT01989676 Active, not recruiting Pfizer November 21, 2013
NCT03013504 Recruiting Prestige Biopharma Pte Ltd January 6, 2017
NCT00398567 Active, not recruiting Puma Biotechnology, Inc. November 10, 2006
NCT01340430 Active, not recruiting Lucia Del Mastro,MD April 22, 2011
NCT01912963 Active, not recruiting Dana-Farber Cancer Institute July 31, 2013
NCT02625441 Recruiting Helsinki University Central Hospital December 9, 2015
NCT02066532 Recruiting Kevin Kalinsky February 19, 2014
NCT03571633 Not yet recruiting Centre Leon Berard June 27, 2018
NCT02656589 Recruiting Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University January 15, 2016
NCT01745965 Active, not recruiting West German Study Group December 10, 2012
NCT00004067 Active, not recruiting NSABP Foundation Inc January 27, 2003
NCT03529110 Not yet recruiting Daiichi Sankyo, Inc. May 18, 2018
NCT03367676 Not yet recruiting Ruijin Hospital December 11, 2017
NCT03084237 Recruiting Shanghai Henlius Biotech March 20, 2017
NCT01104935 Active, not recruiting Comprehensive Support Project for Oncology Research April 16, 2010
NCT00003612 Active, not recruiting Alliance for Clinical Trials in Oncology January 27, 2003
NCT03425656 Recruiting AryoGen Pharmed Co. February 7, 2018
NCT02139358 Active, not recruiting H. Lee Moffitt Cancer Center and Research Institute May 15, 2014
NCT02705859 Recruiting Cancer Trials Ireland March 11, 2016
NCT02614794 Recruiting Cascadian Therapeutics Inc. November 25, 2015
NCT01785420 Recruiting Dr Rajendra A. Badwe February 7, 2013
NCT03414658 Recruiting Ian E. Krop, MD, PhD January 30, 2018
NCT03368729 Not yet recruiting University of Alabama at Birmingham December 11, 2017
NCT01950182 Recruiting Sun Yat-sen University September 25, 2013
NCT02649686 Active, not recruiting Canadian Cancer Trials Group January 7, 2016
NCT03161353 Recruiting MedSIR May 19, 2017
NCT02598310 Recruiting Osaka Medical College November 5, 2015
NCT01570036 Active, not recruiting George E. Peoples April 4, 2012
NCT02162667 Active, not recruiting Celltrion June 13, 2014
NCT01373710 Active, not recruiting Institut Curie June 15, 2011
NCT02488564 Recruiting Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori July 2, 2015
NCT03521245 Recruiting OmicsWay Corp. May 10, 2018
NCT02129556 Active, not recruiting International Breast Cancer Study Group May 2, 2014
NCT02843126 Recruiting Fuda Cancer Hospital, Guangzhou July 25, 2016
NCT02472964 Active, not recruiting Mylan Inc. June 16, 2015
NCT00999804 Active, not recruiting Baylor Breast Care Center October 22, 2009
NCT03135171 Recruiting University of Michigan Cancer Center May 1, 2017
NCT01022086 Recruiting St. Michael's Hospital, Toronto December 1, 2009
NCT01565200 Active, not recruiting Jules Bordet Institute March 28, 2012
NCT03321981 Recruiting Merus N.V. October 26, 2017
NCT02448420 Recruiting SOLTI Breast Cancer Research Group May 19, 2015
NCT01969643 Recruiting Seattle Genetics, Inc. October 25, 2013
NCT02091960 Active, not recruiting Astellas Pharma Global Development, Inc. March 19, 2014
NCT03272477 Recruiting Palleos Healthcare GmbH September 5, 2017
NCT03556358 Recruiting Tanvex BioPharma USA, Inc. June 14, 2018
NCT02214004 Recruiting Gangnam Severance Hospital August 12, 2014
NCT02411344 Recruiting Istituto Oncologico Veneto IRCCS April 8, 2015
NCT03588091 Recruiting Jiangsu HengRui Medicine Co., Ltd. July 17, 2018
NCT01873833 Active, not recruiting University of Southern California June 10, 2013
NCT02080390 Active, not recruiting University of Florida March 6, 2014
NCT01009918 Active, not recruiting University of South Florida November 9, 2009
NCT02492711 Recruiting MacroGenics July 9, 2015
NCT02696707 Recruiting Ottawa Hospital Research Institute March 2, 2016
NCT02568839 Recruiting Thomas Hatschek October 6, 2015
NCT03125928 Recruiting Fox Chase Cancer Center April 24, 2017
NCT02642458 Active, not recruiting University Hospital Tuebingen December 30, 2015
NCT02855775 Recruiting Centre Hospitalier Universitaire de Besancon August 4, 2016
NCT02344472 Recruiting Prof. W. Janni January 26, 2015
NCT02436993 Recruiting University of California, Irvine May 7, 2015
NCT02414646 Active, not recruiting Academic and Community Cancer Research United April 13, 2015
NCT03364348 Recruiting George W. Sledge Jr. December 6, 2017
NCT03262935 Recruiting Synthon Biopharmaceuticals BV August 25, 2017
NCT03062007 Recruiting Biointegrator LLC February 23, 2017
NCT03144947 Recruiting Gruppo Oncologico Italiano di Ricerca Clinica May 9, 2017
NCT02236806 Recruiting Azienda Ospedaliero-Universitaria Careggi September 11, 2014
NCT03025711 Recruiting BELEN RUIZ-ANTORAN January 19, 2017
NCT02689921 Recruiting Midwestern Regional Medical Center February 24, 2016
NCT03304080 Recruiting Icahn School of Medicine at Mount Sinai October 6, 2017
NCT03238495 Recruiting Qamar Khan August 3, 2017
NCT02514681 Recruiting Japan Breast Cancer Research Group August 4, 2015
NCT02789657 Recruiting William Sikov June 3, 2016
NCT03273595 Recruiting Xijing Hospital September 6, 2017
NCT01976169 Recruiting University of Texas Southwestern Medical Center November 5, 2013
NCT02530424 Active, not recruiting Fondazione Michelangelo August 21, 2015
NCT02571530 Recruiting Northwell Health October 8, 2015
NCT02030561 Recruiting National University Hospital, Singapore January 8, 2014
NCT03242551 Recruiting Shenzhen People's Hospital August 8, 2017
NCT03429101 Recruiting Spectrum Pharmaceuticals, Inc February 12, 2018
NCT03058939 Not yet recruiting University of Chicago February 23, 2017
NCT02934828 Recruiting Chinese Academy of Medical Sciences October 17, 2016
NCT03013881 Recruiting United BioPharma January 9, 2017
NCT02910219 Recruiting Georgetown University September 21, 2016
NCT02947685 Recruiting Alliance Foundation Trials, LLC. October 28, 2016
NCT02052102 Recruiting AHS Cancer Control Alberta January 31, 2014
NCT03460067 Recruiting Melissa Mitchell March 9, 2018
NCT03266809 Recruiting Swansea University August 30, 2017
NCT01847001 Active, not recruiting Columbia University May 6, 2013
NCT02541435 Recruiting St. Olavs Hospital September 4, 2015
NCT03006614 Recruiting Shi Yanxia December 30, 2016
NCT01042379 Recruiting QuantumLeap Healthcare Collaborative January 5, 2010
NCT01173341 Recruiting Abramson Cancer Center of the University of Pennsylvania August 2, 2010
NCT02907021 Recruiting Population Health Research Institute September 20, 2016
NCT03500380 Recruiting RemeGen April 17, 2018
NCT02440620 Recruiting Odense University Hospital May 12, 2015
NCT00798070 Active, not recruiting Karolinska University Hospital November 25, 2008
NCT02771938 Recruiting Royal Marsden NHS Foundation Trust May 13, 2016
NCT02674204 Recruiting Cedars-Sinai Medical Center February 4, 2016
NCT03089502 Recruiting University Health Network, Toronto March 24, 2017
NCT03168880 Recruiting Tata Memorial Hospital May 30, 2017
NCT01830244 Active, not recruiting Barwon Health April 12, 2013
NCT03544047 Recruiting Peking Union Medical College June 1, 2018
NCT02624973 Recruiting Haukeland University Hospital December 9, 2015
NCT03437837 Recruiting Peking University First Hospital February 19, 2018
NCT03319459 Recruiting Fate Therapeutics October 24, 2017
NCT03342417 Recruiting ExcellaBio LLC November 17, 2017
NCT01928589 Recruiting Richard Zellars August 26, 2013
NCT02457039 Recruiting The University of Hong Kong May 29, 2015
NCT03530696 Not yet recruiting University of Arizona May 21, 2018
NCT01376505 Recruiting Pravin Kaumaya June 20, 2011
NCT01971515 Active, not recruiting EMD Serono October 29, 2013

Table 4 Clinical trials of HER-2 inhibitors Lapatinib

NCT02073916 Recruiting Jenny C. Chang, MD February 27, 2014
NCT00470704 Active, not recruiting Nancy Lin, MD May 8, 2007
NCT00759642 Active, not recruiting University of Kansas Medical Center September 25, 2008
NCT03085368 Recruiting Peking Union Medical College Hospital March 21, 2017
NCT00331630 Active, not recruiting Northwestern University May 31, 2006
NCT02158507 Active, not recruiting University of Alabama at Birmingham June 9, 2014
NCT00667251 Active, not recruiting Novartis Pharmaceuticals April 28, 2008
NCT00820872 Active, not recruiting Alliance for Clinical Trials in Oncology January 12, 2009
NCT00777101 Active, not recruiting Puma Biotechnology, Inc. October 22, 2008
NCT03080805 Recruiting Jiangsu HengRui Medicine Co., Ltd. March 15, 2017
NCT01875666 Active, not recruiting UNC Lineberger Comprehensive Cancer Center June 12, 2013
NCT01973660 Active, not recruiting SOLTI Breast Cancer Research Group October 31, 2013
NCT01873833 Active, not recruiting University of Southern California June 10, 2013
NCT02362958 Recruiting Sun Yat-sen University February 13, 2015
NCT01273610 Active, not recruiting City of Hope Medical Center January 10, 2011
NCT01619111 Recruiting Prof. W. Janni June 14, 2012
NCT03500380 Recruiting RemeGen April 17, 2018
NCT03273595 Recruiting Xijing Hospital September 6, 2017
NCT03523585 Not yet recruiting Daiichi Sankyo, Inc. May 14, 2018
NCT02768415 Active, not recruiting Chinese Academy of Medical Sciences May 11, 2016
NCT02139358 Active, not recruiting H. Lee Moffitt Cancer Center and Research Institute May 15, 2014
NCT01912963 Active, not recruiting Dana-Farber Cancer Institute July 31, 2013
NCT03262935 Recruiting Synthon Biopharmaceuticals BV August 25, 2017

According to statistics, a total of 117 Herceptin projects targeting breast cancer HER2 are currently in clinical stage, of which 78 are recruiting and 39 are not recruiting.

Table 3 Clinical trials of HER2 inhibitor Lapatinib

Nct id status Lead sponsor study first posted
NCT02073916 Recruiting Jenny C. Chang, MD February 27, 2014
NCT00470704 Active, not recruiting Nancy Lin, MD May 8, 2007
NCT00759642 Active, not recruiting University of Kansas Medical Center September 25, 2008
NCT03085368 Recruiting Peking Union Medical College Hospital March 21, 2017
NCT00331630 Active, not recruiting Northwestern University May 31, 2006
NCT02158507 Active, not recruiting University of Alabama at Birmingham June 9, 2014
NCT00667251 Active, not recruiting Novartis Pharmaceuticals April 28, 2008
NCT00820872 Active, not recruiting Alliance for Clinical Trials in Oncology January 12, 2009
NCT00777101 Active, not recruiting Puma Biotechnology, Inc. October 22, 2008
NCT03080805 Recruiting Jiangsu HengRui Medicine Co., Ltd. March 15, 2017
NCT01875666 Active, not recruiting UNC Lineberger Comprehensive Cancer Center June 12, 2013
NCT01973660 Active, not recruiting SOLTI Breast Cancer Research Group October 31, 2013
NCT01873833 Active, not recruiting University of Southern California June 10, 2013
NCT02362958 Recruiting Sun Yat-sen University February 13, 2015
NCT01273610 Active, not recruiting City of Hope Medical Center January 10, 2011
NCT01619111 Recruiting Prof. W. Janni June 14, 2012
NCT03500380 Recruiting RemeGen April 17, 2018
NCT03273595 Recruiting Xijing Hospital September 6, 2017
NCT03523585 Not yet recruiting Daiichi Sankyo, Inc. May 14, 2018
NCT02768415 Active, not recruiting Chinese Academy of Medical Sciences May 11, 2016
NCT02139358 Active, not recruiting H. Lee Moffitt Cancer Center and Research Institute May 15, 2014
NCT01912963 Active, not recruiting Dana-Farber Cancer Institute July 31, 2013
NCT03262935 Recruiting Synthon Biopharmaceuticals BV August 25, 2017

According to statistics, a total of 23 Lapatinib projects targeting breast cancer HER2 are currently in clinical stage, of which 8 are recruiting and 15 are not recruiting.

Table 4 Clinical trials of EGFR mAB Cetuximab

Nct id Status Lead sponsor study first posted
NCT01097642 Active, not recruiting Jenny C. Chang, MD April 1, 2010
NCT00248287 Active, not recruiting US Oncology Research November 3, 2005
NCT02391727 Recruiting Synermore Biologics Co., Ltd. March 18, 2015
NCT02627274 Recruiting Hoffmann-La Roche December 10, 2015
NCT02124148 Recruiting Eli Lilly and Company April 28, 2014
NCT02318901 Active, not recruiting Western Regional Medical Center December 17, 2014
NCT03319459 Recruiting Fate Therapeutics October 24, 2017
NCT03323424 Not yet recruiting Institut de Cancérologie de la Loire October 27, 2017

Table 5 Clinical trials of KIT inhibitors Sorafenib

Nct id Status Lead sponsor study first posted
NCT00634634 Active, not recruiting Rutgers, The State University of New Jersey March 13, 2008
NCT02624700 Recruiting Virginia Commonwealth University December 8, 2015
NCT00499525 Active, not recruiting Northwestern University July 11, 2007
NCT01724606 Recruiting Memorial Sloan Kettering Cancer Center November 12, 2012

Table 6 Clinical trials of mTOR inhibitors Cisplatin

Nct id Status Lead sponsor study first posted
NCT01674842 Recruiting Dana-Farber Cancer Institute August 29, 2012
NCT00580333 Active, not recruiting Massachusetts General Hospital December 24, 2007
NCT03193853 Recruiting Baylor Research Institute June 21, 2017
NCT02393794 Recruiting Priyanka Sharma March 19, 2015
NCT02422498 Recruiting Memorial Sloan Kettering Cancer Center April 21, 2015
NCT01074970 Active, not recruiting Hoosier Cancer Research Network February 24, 2010
NCT01670500 Recruiting Beth Israel Deaconess Medical Center August 22, 2012
NCT03201861 Recruiting RenJi Hospital June 28, 2017
NCT01931163 Recruiting Jenny C. Chang, MD August 29, 2013
NCT02595905 Recruiting National Cancer Institute (NCI) November 4, 2015
NCT02445391 Recruiting ECOG-ACRIN Cancer Research Group May 15, 2015
NCT01920061 Recruiting Pfizer August 9, 2013
NCT03423849 Not yet recruiting Zhiyong Yu February 6, 2018
NCT01861496 Recruiting Oncology Venture May 23, 2013
NCT03387085 Recruiting NantKwest, Inc. December 29, 2017
NCT02499367 Recruiting The Netherlands Cancer Institute July 16, 2015
NCT03358004 Recruiting Mario Negri Institute for Pharmacological Research November 30, 2017
NCT03006614 Recruiting Shi Yanxia December 30, 2016
NCT02299999 Recruiting UNICANCER November 24, 2014
NCT00003042 Active, not recruiting City of Hope Medical Center January 27, 2003
NCT02393248 Recruiting Incyte Corporation March 19, 2015
NCT03102320 Recruiting Bayer April 5, 2017
NCT02009449 Active, not recruiting ARMO BioSciences December 12, 2013
NCT03058289 Recruiting Intensity Therapeutics, Inc. February 20, 2017
NCT02658214 Recruiting AstraZeneca January 18, 2016

According to statistics, a total of 25 Cisplatin projects targeting breast cancer mTOR are currently in clinical stage, of which 20 are recruiting and 5 are not recruiting.

Table 7 Clinical trials of mTOR inhibitors Erlotinib

Nct id Status Lead sponsor study first posted
NCT00491816 Active, not recruiting University of Kansas Medical Center June 26, 2007
NCT00570258 Active, not recruiting University of Arkansas December 10, 2007
NCT00733408 Active, not recruiting University of Washington August 13, 2008
NCT00600496 Active, not recruiting AstraZeneca January 25, 2008
NCT02071862 Active, not recruiting Calithera Biosciences, Inc February 26, 2014

Table 8 Clinical trials of mTOR inhibitors Temsirolimus

NCT01698918 Active, not recruiting Novartis Pharmaceuticals October 3, 2012
NCT01283789 Active, not recruiting University of Kansas Medical Center January 26, 2011
NCT02531932 Recruiting Amy Tiersten August 25, 2015
NCT01931163 Recruiting Jenny C. Chang, MD August 29, 2013
NCT02520063 Recruiting University of Alabama at Birmingham August 11, 2015
NCT02291913 Active, not recruiting SCRI Development Innovations, LLC November 17, 2014
NCT02344550 Recruiting Asan Medical Center January 26, 2015
NCT02511639 Active, not recruiting Istituto Oncologico Veneto IRCCS July 30, 2015
NCT01805271 Recruiting UNICANCER March 6, 2013
NCT02742051 Recruiting Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University April 18, 2016
NCT02258451 Active, not recruiting Bayer October 7, 2014
NCT02536625 Recruiting Centre Leon Berard September 1, 2015
NCT02642094 Recruiting The University of Texas Health Science Center at San Antonio December 30, 2015
NCT02854618 Recruiting Centre Hospitalier Universitaire de Besancon August 3, 2016
NCT02871791 Recruiting Dana-Farber Cancer Institute August 18, 2016
NCT03154281 Recruiting Avera McKennan Hospital & University Health Center May 16, 2017
NCT02109913 Active, not recruiting VU University Medical Center April 10, 2014
NCT02376985 Recruiting Comprehensive Support Project for Oncology Research March 3, 2015
NCT02120469 Active, not recruiting City of Hope Medical Center April 22, 2014
NCT02216786 Active, not recruiting Queen Mary University of London August 15, 2014
NCT02404051 Recruiting Consorzio Oncotech March 31, 2015
NCT03032406 Recruiting Abramson Cancer Center of the University of Pennsylvania January 26, 2017
NCT02028364 Recruiting Jules Bordet Institute January 7, 2014
NCT01783756 Active, not recruiting Jonsson Comprehensive Cancer Center February 5, 2013
NCT02035813 Recruiting Prof. W. Janni January 14, 2014
NCT01298713 Active, not recruiting ARCAGY/ GINECO GROUP February 18, 2011
NCT02875951 Recruiting KU Leuven August 23, 2016
NCT02057133 Recruiting Eli Lilly and Company February 6, 2014
NCT02123823 Active, not recruiting Boehringer Ingelheim April 28, 2014
NCT02619669 Recruiting Gary Schwartz December 2, 2015
NCT02229136 Active, not recruiting US Oncology Research August 29, 2014
NCT03033186 Recruiting Maastricht University Medical Center January 26, 2017
NCT02646319 Active, not recruiting Mayo Clinic January 5, 2016
NCT02723877 Recruiting PIQUR Therapeutics AG March 31, 2016
NCT03541863 Active, not recruiting Fudan University May 31, 2018
NCT00600496 Active, not recruiting AstraZeneca January 25, 2008
NCT02071862 Active, not recruiting Calithera Biosciences, Inc February 26, 2014

According to statistics, a total of 37 Temsirolimus projects targeting breast cancer mTOR are currently in clinical stage, of which 21 are recruiting and 16 are not recruiting.

Table 8 Clinical trials of mTOR inhibitor Everolumus

Nct id Status Lead sponsor study first posted
NCT02531932 Recruiting Amy Tiersten August 25, 2015
NCT01698918 Active, not recruiting Novartis Pharmaceuticals October 3, 2012
NCT01931163 Recruiting Jenny C. Chang, MD August 29, 2013
NCT02520063 Recruiting University of Alabama at Birmingham August 11, 2015
NCT02291913 Active, not recruiting SCRI Development Innovations, LLC November 17, 2014
NCT02344550 Recruiting Asan Medical Center January 26, 2015
NCT01283789 Active, not recruiting University of Kansas Medical Center January 26, 2011
NCT02511639 Active, not recruiting Istituto Oncologico Veneto IRCCS July 30, 2015
NCT02456857 Recruiting M.D. Anderson Cancer Center May 29, 2015
NCT02742051 Recruiting Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University April 18, 2016
NCT02258451 Active, not recruiting Bayer October 7, 2014
NCT02536625 Recruiting Centre Leon Berard September 1, 2015
NCT02854618 Recruiting Centre Hospitalier Universitaire de Besancon August 3, 2016
NCT01674140 Recruiting Southwest Oncology Group August 28, 2012
NCT02871791 Recruiting Dana-Farber Cancer Institute August 18, 2016
NCT03032406 Recruiting Abramson Cancer Center of the University of Pennsylvania January 26, 2017
NCT02109913 Active, not recruiting VU University Medical Center April 10, 2014
NCT03154281 Recruiting Avera McKennan Hospital & University Health Center May 16, 2017
NCT02216786 Active, not recruiting Queen Mary University of London August 15, 2014
NCT02642094 Recruiting The University of Texas Health Science Center at San Antonio December 30, 2015
NCT02376985 Recruiting Comprehensive Support Project for Oncology Research March 3, 2015
NCT02404051 Recruiting Consorzio Oncotech March 31, 2015
NCT02120469 Active, not recruiting City of Hope Medical Center April 22, 2014
NCT01783756 Active, not recruiting Jonsson Comprehensive Cancer Center February 5, 2013
NCT02028364 Recruiting Jules Bordet Institute January 7, 2014
NCT02035813 Recruiting Prof. W. Janni January 14, 2014
NCT02875951 Recruiting KU Leuven August 23, 2016
NCT02057133 Recruiting Eli Lilly and Company February 6, 2014
NCT01298713 Active, not recruiting ARCAGY/ GINECO GROUP February 18, 2011
NCT02123823 Active, not recruiting Boehringer Ingelheim April 28, 2014
NCT02229136 Active, not recruiting US Oncology Research August 29, 2014
NCT02619669 Recruiting Gary Schwartz December 2, 2015
NCT03033186 Recruiting Maastricht University Medical Center January 26, 2017
NCT02646319 Active, not recruiting Mayo Clinic January 5, 2016
NCT03541863 Active, not recruiting Fudan University May 31, 2018
NCT02723877 Recruiting PIQUR Therapeutics AG March 31, 2016
NCT02071862 Active, not recruiting Calithera Biosciences, Inc February 26, 2014
NCT00600496 Active, not recruiting AstraZeneca January 25, 2008

According to statistics, a total of 38 Everolumus projects targeting breast cancer mTOR are currently in clinical stage, of which 22 are recruiting and 16 are not recruiting.

3.3 Breast cancer therapy for Notch pathway

Notch receptors and ligands may be inhibited by selective strategiessuch as g-secretase inhibitors RO4929097, GSIs show antitumor activity in several human cancer cell lines. Xenograft studies with glioblastoma and lung adenocarcinoma cell lines have shown that GSIs reduced both tumor growth and vasculature, induced growth arrest of T-ALL cells, and induced apoptosis in melanoma cell lines.

3.4 Breast cancer therapy for Wnt pathway

Several Wnt/β-catenin target genes have been identified, including those that control cell proliferation and apoptosis, thus mediating cancer initiation and progression. In addition to this, Salinomycin and Nigericin, act as inhibitors of the Wnt/βcatenin signaling pathway by inducing degradation of LRP6, and are selective breast cancer stem cell killers.

3.5 Breast cancer therapy for estrogen pathway

The estrogens first penetrate through the cell membrane and then bind to the estrogen receptor monomer, which is then dimerized and transported into the nucleus to activate signaling. Treatment with tamoxifen blocks the binding of estrogen and, thus, inhibits the estrogen-activated signaling. Treatment with Fulvestrant inhibits the cytoplasmic dimerization of estrogen. Treatment with aromatase inhibitors, such as Letrozole, Anastrozole and Exemestane blocks estrogen production. Another characteristic correlated to the ER pathway is the progesterone receptor (PR) signaling, which is also involved in the regulation of luminal type breast cancer development.

Table 9 Clinical trials of ER inhibitor Letrozole

Nct id Status Lead sponsor study first posted
NCT02619162 Recruiting Centro Nacional de Investigaciones Oncologicas CARLOS III December 2, 2015
NCT02600923 Recruiting Pfizer November 9, 2015
NCT02712723 Recruiting Qamar Khan March 18, 2016
NCT03054363 Recruiting University of Colorado, Denver February 15, 2017
NCT00553410 Active, not recruiting International Breast Cancer Study Group November 5, 2007
NCT02802748 Recruiting SOLTI Breast Cancer Research Group June 16, 2016
NCT02619669 Recruiting Gary Schwartz December 2, 2015
NCT00382070 Active, not recruiting NSABP Foundation Inc September 28, 2006
NCT01064635 Active, not recruiting IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy February 8, 2010
NCT00634634 Active, not recruiting Rutgers, The State University of New Jersey March 13, 2008
NCT03481998 Recruiting Jiangsu HengRui Medicine Co., Ltd. March 29, 2018
NCT00338728 Active, not recruiting M.D. Anderson Cancer Center June 20, 2006
NCT01791985 Active, not recruiting Imperial College London February 15, 2013
NCT03507465 Recruiting Guangdong General Hospital April 25, 2018
NCT03306472 Recruiting Cambridge University Hospitals NHS Foundation Trust October 11, 2017
NCT00651976 Recruiting Vanderbilt-Ingram Cancer Center April 3, 2008
NCT02491983 Active, not recruiting MedSIR July 8, 2015
NCT01035099 Recruiting Weill Medical College of Cornell University December 18, 2009
NCT02742051 Recruiting Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University April 18, 2016
NCT01870505 Active, not recruiting Memorial Sloan Kettering Cancer Center June 6, 2013
NCT03497702 Recruiting National Cancer Center, Korea April 13, 2018
NCT02692755 Recruiting Georgetown University February 26, 2016
NCT03283384 Recruiting Borstkanker Onderzoek Groep September 14, 2017
NCT02661932 Recruiting Erasme University Hospital January 25, 2016
NCT00412022 Active, not recruiting National Cancer Institute, Naples December 15, 2006
NCT00541086 Active, not recruiting Gruppo Italiano Mammella (GIM) October 8, 2007
NCT01589367 Recruiting Seoul National University Hospital May 1, 2012
NCT02115048 Active, not recruiting Translational Research in Oncology April 15, 2014
NCT02400567 Active, not recruiting UNICANCER March 27, 2015
NCT02214004 Recruiting Gangnam Severance Hospital August 12, 2014
NCT02958852 Recruiting Lund University Hospital November 8, 2016
NCT02730091 Recruiting Centre Hospitalier Universitaire de Besancon April 6, 2016
NCT02778685 Recruiting City of Hope Medical Center May 20, 2016
NCT01381874 Active, not recruiting Janssen Research & Development, LLC June 27, 2011
NCT02411344 Active, not recruiting Istituto Oncologico Veneto IRCCS April 8, 2015
NCT02538484 Recruiting Andrew Brenner September 2, 2015
NCT02246621 Active, not recruiting Eli Lilly and Company September 23, 2014
NCT03128619 Recruiting Jonsson Comprehensive Cancer Center April 25, 2017
NCT02585388 Active, not recruiting ARCAGY/ GINECO GROUP October 23, 2015
NCT02583828 Recruiting Capital Medical University October 22, 2015
NCT02455154 Recruiting Shanghai Jiao Tong University School of Medicine May 27, 2015
NCT02769104 Recruiting Zhejiang Cancer Hospital May 11, 2016
NCT02767661 Recruiting Sun Yat-sen University May 10, 2016
NCT02806050 Active, not recruiting University Medical Center Groningen June 20, 2016
NCT01466972 Active, not recruiting Hope Rugo, MD November 8, 2011
NCT02109913 Active, not recruiting VU University Medical Center April 10, 2014
NCT01674140 Recruiting Southwest Oncology Group August 28, 2012
NCT02910050 Recruiting Xu fei September 21, 2016
NCT01478477 Active, not recruiting Ohio State University Comprehensive Cancer Center November 23, 2011
NCT03324932 Recruiting Kyoto Prefectural University of Medicine October 30, 2017
NCT00999804 Active, not recruiting Baylor Breast Care Center October 22, 2009
NCT02701348 Recruiting NHS Tayside March 8, 2016
NCT03355157 Not yet recruiting German Breast Group November 28, 2017
NCT02221999 Recruiting RenJi Hospital August 21, 2014
NCT03373708 Not yet recruiting Zhiyong Yu December 14, 2017
NCT02894398 Recruiting iOMEDICO AG September 9, 2016
NCT02947685 Recruiting Alliance Foundation Trials, LLC. October 28, 2016
NCT03024580 Recruiting Instituto Nacional de Cancer, Brazil January 19, 2017
NCT00463489 Active, not recruiting Ontario Clinical Oncology Group (OCOG) April 20, 2007
NCT02338310 Active, not recruiting Institute of Cancer Research, United Kingdom January 14, 2015
NCT02291913 Active, not recruiting SCRI Development Innovations, LLC November 17, 2014
NCT03238703 Not yet recruiting Fred Hutchinson Cancer Research Center August 3, 2017
NCT03058939 Not yet recruiting University of Chicago February 23, 2017
NCT01989780 Active, not recruiting Japan Breast Cancer Research Group November 21, 2013
NCT02890082 Recruiting Institut Cancerologie de l'Ouest September 7, 2016
NCT02689921 Recruiting Midwestern Regional Medical Center February 24, 2016
NCT03219476 Recruiting Medical College of Wisconsin July 17, 2017
NCT03111615 Not yet recruiting Centro Hospitalar Lisboa Ocidental April 13, 2017
NCT02269670 Active, not recruiting Emory University October 21, 2014
NCT03272477 Recruiting Palleos Healthcare GmbH September 5, 2017
NCT02592746 Recruiting Samsung Medical Center October 30, 2015
NCT02344472 Recruiting Prof. W. Janni January 26, 2015
NCT02995772 Recruiting Dharmais National Cancer Center Hospital December 16, 2016
NCT02603679 Recruiting Thomas Hatschek November 13, 2015
NCT02624973 Recruiting Haukeland University Hospital December 9, 2015
NCT03384095 Not yet recruiting Erin Newton December 27, 2017
NCT03321981 Recruiting Merus N.V. October 26, 2017

According to statistics, a total of 77 Letrozole projects targeting breast cancer ER are currently in clinical stage, of which 45 are recruiting and 32 are not recruiting.

Table 10 Clinical trials of ER inhibitors Tamoxifen

Nct id Status Lead sponsor study first posted
NCT02488603 Not yet recruiting National Cancer Center, Korea July 2, 2015
NCT02890082 Recruiting Institut Cancerologie de l'Ouest September 7, 2016
NCT03351062 Recruiting Chinese Anti-Cancer Association November 22, 2017
NCT01196936 Active, not recruiting University of Alabama at Birmingham September 9, 2010
NCT02988986 Active, not recruiting Jenny C. Chang, MD December 12, 2016
NCT02936206 Recruiting Icahn School of Medicine at Mount Sinai October 18, 2016
NCT03504631 Recruiting Trisakti University April 20, 2018
NCT03573648 Not yet recruiting Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins June 29, 2018
NCT02344940 Active, not recruiting Shanghai Jiao Tong University School of Medicine January 26, 2015
NCT01638247 Active, not recruiting German Breast Group July 11, 2012
NCT02913430 Recruiting Rachel Jankowitz September 23, 2016
NCT03582865 Not yet recruiting Assiut University July 11, 2018
NCT01579734 Active, not recruiting European Institute of Oncology April 18, 2012
NCT02747004 Active, not recruiting Eli Lilly and Company April 21, 2016
NCT00301457 Active, not recruiting Maastricht University Medical Center March 13, 2006
NCT03423199 Recruiting National Cancer Center, Japan February 6, 2018
NCT02062489 Recruiting Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University February 13, 2014
NCT00541086 Active, not recruiting Gruppo Italiano Mammella (GIM) October 8, 2007
NCT00072462 Active, not recruiting Queen Mary University of London November 6, 2003
NCT02914158 Recruiting First Affiliated Hospital, Sun Yat-Sen University September 26, 2016
NCT00066703 Active, not recruiting International Breast Cancer Study Group August 7, 2003
NCT00412022 Active, not recruiting National Cancer Institute, Naples December 15, 2006
NCT02355600 Recruiting Instituto de Investigacion Sanitaria La Fe February 4, 2015
NCT02970682 Recruiting Evgen Pharma November 22, 2016
NCT02668666 Recruiting Oana Danciu, MD January 29, 2016
NCT00538330 Active, not recruiting King Faisal Specialist Hospital & Research Center October 2, 2007
NCT02384239 Recruiting University of California, San Francisco March 10, 2015
NCT02819921 Recruiting Seoul National University Hospital June 30, 2016
NCT02132000 Recruiting Fengxi Su May 6, 2014
NCT03381963 Recruiting University Hospital, Geneva December 22, 2017
NCT03211572 Not yet recruiting Ottawa Hospital Research Institute July 7, 2017
NCT00738777 Recruiting The Netherlands Cancer Institute August 20, 2008
NCT00003857 Active, not recruiting Radiation Therapy Oncology Group January 27, 2003
NCT01064635 Active, not recruiting IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy February 8, 2010
NCT02866955 Recruiting Institut de Cancérologie de Lorraine August 15, 2016
NCT02395627 Recruiting Pamela Munster March 23, 2015
NCT00886535 Active, not recruiting Milton S. Hershey Medical Center April 23, 2009
NCT01298713 Active, not recruiting ARCAGY/ GINECO GROUP February 18, 2011
NCT03137368 Recruiting Cancer Institute and Hospital, Chinese Academy of Medical Sciences May 2, 2017
NCT02097459 Recruiting Peking Union Medical College Hospital March 27, 2014
NCT01973660 Active, not recruiting SOLTI Breast Cancer Research Group October 31, 2013
NCT03373708 Not yet recruiting Zhiyong Yu December 14, 2017
NCT03494400 Not yet recruiting Universidade Estadual Paulista Júlio de Mesquita Filho April 11, 2018
NCT02630693 Active, not recruiting Canadian Cancer Trials Group December 15, 2015
NCT02467686 Recruiting Irmandade da Santa Casa de Misericordia de Sao Paulo June 10, 2015
NCT01564056 Active, not recruiting UNICANCER March 27, 2012
NCT03518138 Not yet recruiting Que Oncology May 8, 2018
NCT03219476 Recruiting Medical College of Wisconsin July 17, 2017
NCT01266213 Active, not recruiting Samsung Medical Center December 24, 2010
NCT02995772 Recruiting Dharmais National Cancer Center Hospital December 16, 2016
NCT03024580 Recruiting Instituto Nacional de Cancer, Brazil January 19, 2017
NCT03161353 Recruiting MedSIR May 19, 2017
NCT00003042 Active, not recruiting City of Hope Medical Center January 27, 2003
NCT02476786 Recruiting Washington University School of Medicine June 19, 2015
NCT02291913 Active, not recruiting SCRI Development Innovations, LLC November 17, 2014
NCT02603679 Recruiting Thomas Hatschek November 13, 2015
NCT03592771 Not yet recruiting University of Tennessee July 19, 2018
NCT00129935 Active, not recruiting Spanish Breast Cancer Research Group August 12, 2005
NCT03238703 Not yet recruiting Fred Hutchinson Cancer Research Center August 3, 2017
NCT03058939 Not yet recruiting University of Chicago February 23, 2017
NCT01791829 Active, not recruiting Ontario Clinical Oncology Group (OCOG) February 15, 2013
NCT01530373 Recruiting University of Arkansas February 9, 2012
NCT03280563 Recruiting Hoffmann-La Roche September 12, 2017
NCT00193726 Recruiting Sudeep Gupta September 19, 2005
NCT02290782 Recruiting Universitätsmedizin Mannheim November 14, 2014
NCT02850939 Recruiting The University of Texas Health Science Center at San Antonio August 1, 2016
NCT03065621 Recruiting Jules Bordet Institute February 28, 2017
NCT02344472 Recruiting Prof. W. Janni January 26, 2015
NCT02771938 Recruiting Royal Marsden NHS Foundation Trust May 13, 2016
NCT01745965 Active, not recruiting West German Study Group December 10, 2012
NCT03272477 Recruiting Palleos Healthcare GmbH September 5, 2017
NCT02624973 Recruiting Haukeland University Hospital December 9, 2015
NCT00887380 Active, not recruiting Trans-Tasman Radiation Oncology Group (TROG) April 24, 2009
NCT01831076 Active, not recruiting University of Colorado, Denver April 15, 2013
NCT01971515 Active, not recruiting EMD Serono October 29, 2013

According to statistics, a total of 75 Tamoxifen projects targeting breast cancer ER are currently in clinical stage, of which 37 are recruiting and 38 are not recruiting.

Table 11 Clinical trials of ER inhibitors Fulvestrant

Nct id Status Lead sponsor study first posted
NCT02953860 Recruiting University of Colorado, Denver November 3, 2016
NCT03289039 Recruiting Dana-Farber Cancer Institute September 20, 2017
NCT02738866 Recruiting Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins April 14, 2016
NCT02936206 Recruiting Icahn School of Medicine at Mount Sinai October 18, 2016
NCT03386162 Not yet recruiting UNICANCER December 29, 2017
NCT03393845 Recruiting Nancy Chan, MD January 9, 2018
NCT00570323 Active, not recruiting Mothaffar Rimawi December 10, 2007
NCT03344536 Recruiting Memorial Sloan Kettering Cancer Center November 17, 2017
NCT02646735 Recruiting Chinese Academy of Medical Sciences January 6, 2016
NCT02437318 Active, not recruiting Novartis Pharmaceuticals May 7, 2015
NCT02909361 Recruiting Fudan University September 21, 2016
NCT00921115 Active, not recruiting University of Kansas Medical Center June 16, 2009
NCT03241810 Recruiting Merrimack Pharmaceuticals August 8, 2017
NCT03591549 Not yet recruiting Assiut University July 19, 2018
NCT03507088 Recruiting Zhimin Shao April 24, 2018
NCT02958852 Recruiting Lund University Hospital November 8, 2016
NCT02913430 Recruiting Rachel Jankowitz September 23, 2016
NCT02569801 Active, not recruiting Genentech, Inc. October 7, 2015
NCT03238196 Recruiting Vanderbilt-Ingram Cancer Center August 3, 2017
NCT00075764 Active, not recruiting Southwest Oncology Group January 13, 2004
NCT02000193 Active, not recruiting Sun Yat-sen University December 4, 2013
NCT01992952 Active, not recruiting Velindre NHS Trust November 25, 2013
NCT02491983 Active, not recruiting MedSIR July 8, 2015
NCT02340221 Active, not recruiting Hoffmann-La Roche January 16, 2015
NCT02632045 Recruiting Kevin Kalinsky December 16, 2015
NCT00451555 Active, not recruiting Eli Lilly and Company March 23, 2007
NCT02983604 Active, not recruiting Gilead Sciences December 6, 2016
NCT00570258 Active, not recruiting University of Arkansas December 10, 2007
NCT02028507 Recruiting Spanish Breast Cancer Research Group January 7, 2014
NCT00585507 Active, not recruiting Beth Israel Deaconess Medical Center January 3, 2008
NCT03560856 Not yet recruiting Assistance Publique - Hôpitaux de Paris June 18, 2018
NCT03322215 Recruiting Theodoros Foukakis October 26, 2017
NCT02684032 Recruiting Pfizer February 17, 2016
NCT02216786 Active, not recruiting Queen Mary University of London August 15, 2014
NCT00816582 Recruiting British Columbia Cancer Agency January 1, 2009
NCT02692755 Recruiting Georgetown University February 26, 2016
NCT03447132 Recruiting International Cancer Research Group, United Arab Emirates February 27, 2018
NCT02384746 Recruiting Dartmouth-Hitchcock Medical Center March 10, 2015
NCT02536742 Recruiting International Breast Cancer Study Group September 1, 2015
NCT02894398 Recruiting iOMEDICO AG September 9, 2016
NCT02626507 Recruiting Hoffman Oncology December 10, 2015
NCT01441947 Active, not recruiting Massachusetts General Hospital September 28, 2011
NCT02983071 Recruiting G1 Therapeutics, Inc. December 6, 2016
NCT03192293 Recruiting National University Hospital, Singapore June 20, 2017
NCT01142401 Active, not recruiting National Cancer Institute (NCI) June 11, 2010
NCT02970682 Recruiting Evgen Pharma November 22, 2016
NCT02384239 Recruiting University of California, San Francisco March 10, 2015
NCT02219789 Active, not recruiting Mayo Clinic August 19, 2014
NCT02760030 Recruiting Ohio State University Comprehensive Cancer Center May 3, 2016
NCT02964507 Recruiting GlaxoSmithKline November 16, 2016
NCT03425838 Recruiting Borstkanker Onderzoek Groep February 8, 2018
NCT00738777 Recruiting The Netherlands Cancer Institute August 20, 2008
NCT03430466 Recruiting Kyoto Breast Cancer Research Network February 13, 2018
NCT02540330 Recruiting Atossa Genetics, Inc. September 3, 2015
NCT03220178 Recruiting Palleos Healthcare GmbH July 18, 2017
NCT01266213 Active, not recruiting Samsung Medical Center December 24, 2010
NCT02530424 Active, not recruiting Fondazione Michelangelo August 21, 2015
NCT02630693 Active, not recruiting Canadian Cancer Trials Group December 15, 2015
NCT03099174 Recruiting Boehringer Ingelheim April 4, 2017
NCT03355157 Not yet recruiting German Breast Group November 28, 2017
NCT02947685 Recruiting Alliance Foundation Trials, LLC. October 28, 2016
NCT03024580 Recruiting Instituto Nacional de Cancer, Brazil January 19, 2017
NCT01989780 Active, not recruiting Japan Breast Cancer Research Group November 21, 2013
NCT03134638 Recruiting Syros Pharmaceuticals May 1, 2017
NCT03195192 Recruiting Translational Drug Development June 22, 2017
NCT02269670 Active, not recruiting Emory University October 21, 2014
NCT03204734 Recruiting Zhejiang Cancer Hospital July 2, 2017
NCT02344472 Recruiting Prof. W. Janni January 26, 2015
NCT03321981 Recruiting Merus N.V. October 26, 2017

According to statistics, a total of 69 Fulvestrant projects targeting breast cancer ER are currently in clinical stage, of which 43 are recruiting and 26 are not recruiting.

Table 12 Clinical trials of ER inhibitors Anastrozole

Nct id Status Lead sponsor study first posted
NCT00078832 Active, not recruiting Queen Mary University of London March 9, 2004
NCT00301457 Active, not recruiting Maastricht University Medical Center March 13, 2006
NCT00570323 Active, not recruiting Mothaffar Rimawi December 10, 2007
NCT01791985 Active, not recruiting Imperial College London February 15, 2013
NCT00075764 Active, not recruiting Southwest Oncology Group January 13, 2004
NCT00921115 Active, not recruiting University of Kansas Medical Center June 16, 2009
NCT00265759 Active, not recruiting Alliance for Clinical Trials in Oncology December 15, 2005
NCT00887380 Active, not recruiting Trans-Tasman Radiation Oncology Group (TROG) April 24, 2009
NCT00541086 Active, not recruiting Gruppo Italiano Mammella (GIM) October 8, 2007
NCT02942355 Recruiting Antoinette Tan October 24, 2016
NCT01723774 Recruiting Washington University School of Medicine November 8, 2012
NCT02440230 Recruiting Shanghai Jiao Tong University School of Medicine May 12, 2015
NCT02730091 Recruiting Centre Hospitalier Universitaire de Besancon April 6, 2016
NCT02089854 Recruiting Peking Union Medical College Hospital March 18, 2014
NCT01381874 Active, not recruiting Janssen Research & Development, LLC June 27, 2011
NCT00738777 Recruiting The Netherlands Cancer Institute August 20, 2008
NCT02585388 Active, not recruiting ARCAGY/ GINECO GROUP October 23, 2015
NCT03304080 Recruiting Icahn School of Medicine at Mount Sinai October 6, 2017
NCT02206984 Recruiting Rachel Jankowitz August 1, 2014
NCT02918084 Recruiting IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy September 28, 2016
NCT02767661 Recruiting Sun Yat-sen University May 10, 2016
NCT02511639 Active, not recruiting Istituto Oncologico Veneto IRCCS July 30, 2015
NCT01266213 Active, not recruiting Samsung Medical Center December 24, 2010
NCT01466972 Active, not recruiting Hope Rugo, MD November 8, 2011
NCT03425838 Recruiting Borstkanker Onderzoek Groep February 8, 2018
NCT02109913 Active, not recruiting VU University Medical Center April 10, 2014
NCT01478477 Active, not recruiting Ohio State University Comprehensive Cancer Center November 23, 2011
NCT02910050 Recruiting Xu fei September 21, 2016
NCT02648477 Recruiting City of Hope Medical Center January 7, 2016
NCT02947685 Recruiting Alliance Foundation Trials, LLC. October 28, 2016
NCT02894398 Recruiting iOMEDICO AG September 9, 2016
NCT03099174 Recruiting Boehringer Ingelheim April 4, 2017
NCT02188745 Recruiting Dartmouth-Hitchcock Medical Center July 14, 2014
NCT03024580 Recruiting Instituto Nacional de Cancer, Brazil January 19, 2017
NCT02532400 Recruiting Ruijin Hospital August 25, 2015
NCT03554044 Not yet recruiting University of California, San Francisco June 12, 2018
NCT03324932 Recruiting Kyoto Prefectural University of Medicine October 30, 2017
NCT02995772 Recruiting Dharmais National Cancer Center Hospital December 16, 2016
NCT03555877 Recruiting German Breast Group June 14, 2018
NCT01989780 Active, not recruiting Japan Breast Cancer Research Group November 21, 2013
NCT02040857 Active, not recruiting Dana-Farber Cancer Institute January 20, 2014
NCT02689921 Recruiting Midwestern Regional Medical Center February 24, 2016
NCT00256217 Active, not recruiting Rita Sanghvi, Mehta November 21, 2005
NCT03184090 Recruiting MedSIR June 12, 2017
NCT03238703 Not yet recruiting Fred Hutchinson Cancer Research Center August 3, 2017
NCT03219476 Recruiting Medical College of Wisconsin July 17, 2017
NCT02269670 Active, not recruiting Emory University October 21, 2014
NCT03272477 Recruiting Palleos Healthcare GmbH September 5, 2017
NCT03204734 Recruiting Zhejiang Cancer Hospital July 2, 2017
NCT02344472 Recruiting Prof. W. Janni January 26, 2015
NCT00556374 Active, not recruiting Amgen November 12, 2007
NCT02236572 Active, not recruiting Yale University September 10, 2014
NCT02603679 Recruiting Thomas Hatschek November 13, 2015
NCT03384095 Not yet recruiting Erin Newton December 27, 2017
NCT03321981 Recruiting Merus N.V. October 26, 2017
NCT02476955 Recruiting ArQule June 22, 2015

According to statistics, a total of 56 Anastrozole projects targeting breast cancer ER are currently in clinical stage, of which 31 are recruiting and 25 are not recruiting.

Table 13 Clinical trials of ER inhibitors Exemestane

Nct id Status Lead sponsor study first posted
NCT00810797 Active, not recruiting City of Hope Medical Center December 18, 2008
NCT02482753 Active, not recruiting Chipscreen Biosciences, Ltd. June 26, 2015
NCT01783444 Active, not recruiting Novartis Pharmaceuticals February 5, 2013
NCT03308201 Recruiting Tianjin Hemay Pharmaceutical Co.,Ltd October 12, 2017
NCT02646735 Recruiting Chinese Academy of Medical Sciences January 6, 2016
NCT02820961 Active, not recruiting Syndax Pharmaceuticals July 1, 2016
NCT02990845 Not yet recruiting National Taiwan University Hospital December 13, 2016
NCT02676986 Recruiting Queen Mary University of London February 9, 2016
NCT02258451 Active, not recruiting Bayer October 7, 2014
NCT00066703 Active, not recruiting International Breast Cancer Study Group August 7, 2003
NCT00265759 Active, not recruiting Alliance for Clinical Trials in Oncology December 15, 2005
NCT02983604 Active, not recruiting Gilead Sciences December 6, 2016
NCT02623751 Active, not recruiting Kyowa Hakko Kirin Co., Ltd December 8, 2015
NCT00541086 Active, not recruiting Gruppo Italiano Mammella (GIM) October 8, 2007
NCT02917005 Not yet recruiting Hamdy A. Azim September 28, 2016
NCT01381874 Active, not recruiting Janssen Research & Development, LLC June 27, 2011
NCT02440230 Recruiting Shanghai Jiao Tong University School of Medicine May 12, 2015
NCT02871791 Recruiting Dana-Farber Cancer Institute August 18, 2016
NCT01655004 Recruiting National University Hospital, Singapore August 1, 2012
NCT01594216 Active, not recruiting Abramson Cancer Center of the University of Pennsylvania May 9, 2012
NCT03538171 Recruiting EddingPharm Oncology Co., LTD. May 28, 2018
NCT02592746 Recruiting Samsung Medical Center October 30, 2015
NCT02109913 Active, not recruiting VU University Medical Center April 10, 2014
NCT02404051 Recruiting Consorzio Oncotech March 31, 2015
NCT02598557 Recruiting National Cancer Institute (NCI) November 6, 2015
NCT01144468 Active, not recruiting University Health Network, Toronto June 15, 2010
NCT02444390 Recruiting UNICANCER May 14, 2015
NCT02028364 Recruiting Jules Bordet Institute January 7, 2014
NCT03137368 Recruiting Cancer Institute and Hospital, Chinese Academy of Medical Sciences May 2, 2017
NCT02918084 Recruiting IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy September 28, 2016
NCT01831076 Active, not recruiting University of Colorado, Denver April 15, 2013
NCT02875951 Recruiting KU Leuven August 23, 2016
NCT02767661 Recruiting Sun Yat-sen University May 10, 2016
NCT02511639 Active, not recruiting Istituto Oncologico Veneto IRCCS July 30, 2015
NCT02057133 Recruiting Eli Lilly and Company February 6, 2014
NCT02291913 Active, not recruiting SCRI Development Innovations, LLC November 17, 2014
NCT03125746 Recruiting Shandong Luoxin Pharmaceutical Group Stock Co., Ltd. April 24, 2017
NCT01674140 Recruiting Southwest Oncology Group August 28, 2012
NCT02910050 Recruiting Xu fei September 21, 2016
NCT02123823 Active, not recruiting Boehringer Ingelheim April 28, 2014
NCT02188745 Recruiting Dartmouth-Hitchcock Medical Center July 14, 2014
NCT03361800 Recruiting UNC Lineberger Comprehensive Cancer Center December 5, 2017
NCT03554044 Not yet recruiting University of California, San Francisco June 12, 2018
NCT02532400 Recruiting Ruijin Hospital August 25, 2015
NCT03024580 Recruiting Instituto Nacional de Cancer, Brazil January 19, 2017
NCT03238703 Not yet recruiting Fred Hutchinson Cancer Research Center August 3, 2017
NCT03184090 Recruiting MedSIR June 12, 2017
NCT01989780 Active, not recruiting Japan Breast Cancer Research Group November 21, 2013
NCT02476786 Recruiting Washington University School of Medicine June 19, 2015
NCT02689921 Recruiting Midwestern Regional Medical Center February 24, 2016
NCT03219476 Recruiting Medical College of Wisconsin July 17, 2017
NCT03280563 Recruiting Hoffmann-La Roche September 12, 2017
NCT01937052 Active, not recruiting Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins September 9, 2013
NCT03272477 Recruiting Palleos Healthcare GmbH September 5, 2017
NCT02467686 Recruiting Irmandade da Santa Casa de Misericordia de Sao Paulo June 10, 2015
NCT03204734 Recruiting Zhejiang Cancer Hospital July 2, 2017
NCT02344472 Recruiting Prof. W. Janni January 26, 2015
NCT02236572 Active, not recruiting Yale University September 10, 2014
NCT02376985 Recruiting Comprehensive Support Project for Oncology Research March 3, 2015
NCT02995772 Recruiting Dharmais National Cancer Center Hospital December 16, 2016
NCT02947685 Recruiting Alliance Foundation Trials, LLC. October 28, 2016
NCT02603679 Recruiting Thomas Hatschek November 13, 2015
NCT03321981 Recruiting Merus N.V. October 26, 2017

According to statistics, a total of 63 Exemestane projects targeting breast cancer ER are currently in clinical stage, of which 38 are recruiting and 25 are not recruiting.

References:

  1. Zhang M H.; et al. Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials[J]. Biomedical reports. 2014, 2(1): 41-52.
  2. Kamdje A H N.; et al. Signaling pathways in breast cancer: therapeutic targeting of the microenvironment[J]. Cellular signalling. 2014, 26(12): 2843-2856.
  3. Banin Hirata B K.; et al. Molecular markers for breast cancer: prediction on tumor behavior[J]. Disease markers. 2014.
  4. Narod S A, Foulkes W D. BRCA1 and BRCA2: 1994 and beyond[J]. Nature Reviews Cancer. 2014, 4(9): 665.
  5. McDonald E S.; et al. Clinical diagnosis and management of breast cancer[J]. J Nucl Med. 2016, 57(Suppl 1): 9S-16S.
  6. P Kourea H. Targeted pathways in breast cancer: molecular and protein markers guiding therapeutic decisions[J]. Current molecular pharmacology. 2014, 7(1): 4-21.
  7. Higgins M J, Baselga J. Targeted therapies for breast cancer[J]. The Journal of clinical investigation. 2011, 121(10): 3797-3803.
For research use only. Not intended for any clinical use.