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Published: March 2017
Report Code: LS10796
Category : Pharmaceuticals
Estrogen Receptor-Positive (ER+) breast cancer is the most common type of breast cancer diagnosed and it refers to the cancer cells that have receptors on their surface to bind with estrogen. Breast cancer is said to be estrogen receptor-positive (ER+), if it contains estrogen that receives signals from estrogen to promote cell growth. Breast cancer is a syndrome that affects breast tissues and cells in the breast grow in an uncontrollable manner forming a tumor, which can be felt as a lump or can be viewed under x-ray. Majority of breast cancers begin in lobules, tissues which are made up of glands for milk production and ducts that connect the lobules to the nipple. The risk factor of the disease includes personal or family medical history or certain changes in their genes. The increased life expectancy, shift toward urbanization and adoption of western lifestyles are the common factors instigating the risk of development of breast cancer. Early detection of ER+ breast cancer is important for the improvement of breast cancer outcome and survival.
Breast cancer still remains the major cause of deaths among women, but in coming years, it is likely that mortality and morbidity would increase in much less proportion than the standard reckoning, and there is even a possibility of decrease in the rate of occurrence of the disease. There are several reasons that are likely to contribute to the same, such as progress in screening/diagnosis, which leads to early detection of the tumor, making it more acquiescent for treatment.
The second reason can be progress in the pharmacological treatment and incursion of new drugs such as tamoxifen, which have been highly effective in the treatment of contralateral breast cancer in ER+ patients.
Thirdly, the pipeline is very profuse; new therapeutic agents are under development, which are likely to become available in next few years.
As of February 2017, the ER+ breast cancer pipeline comprised of approximately 74 drug candidates, of which nine are in Phase III stage, 16 in Phase II stage, 18 is in Phase I stage, and three in the Pre- Clinical stage. The development of 14 ER+ breast cancer candidates was found to be inactive and 14 products were discontinued.
NUMBER OF ER+ BREAST CANCER DRUG CANDIDATES UNDER DEVELOPMENT (2017)
Based on target, it was found that around 7.0% drug candidates target phosphatidylinositol-3-kinase (PI3K), 7.0% of the drug candidates target mammalian target of rapamycin (mTOR), 6.0% drug candidates target bromodomain and extra-terminal (BET) inhibitors, 4.0% of the drug candidates target cyclin-dependent kinases (CDK), 4.0% of the drug candidates target histone deacetylase (HDAC) and 72.0% of the drug candidates target others, including but not limited to, lymphocyte-activation gene 3 (LAG3), human epidermal growth factor receptor 2 (HER2), steroidal enzyme 17α-hydroxylase and c17-20 lyase, fibroblast growth factor receptor (FGFR), androgen receptor, DNA methyltransferase, and vascular endothelial growth factor receptor (VEGFR).
Pharma giants such as Chipscreen Biosciences, Ltd., Novartis AG, Syndax Pharmaceuticals, Tesaro, Inc., Eli Lily & Company, Genentech, Inc. and AstraZeneca plc are actively involved in the development drugs for the treatment of ER+ breast cancer. Ribociclib is being developed by Novartis Pharmaceuticals, in Phase III clinical stage for the treatment of ER+ breast cancer. It is a small molecule administered by oral route and inhibits CDK4/6.
Chipscreen Biosciences, Ltd. is using chemo genomics approach for the development of Chidamide for ER+ breast cancer. For the discovery of small molecules, the company is applying a comprehensive systemic approach, integrated with in silico design, chemistries, high content screening, global gene expression profiling, and informatics in early stage of the discovery.
Several companies are involved in the development of ER+ breast cancer pipeline, with their products in different phases. Novartis AG is developing five products, out of which two are in Phase I and three in Phase III stage. AstraZeneca plc is developing three products, which are in Phase II. Genentech, Inc., Eli Lily & Company and Astellas Pharma Inc., each have their candidate in Phase III stage of development. Bayer AG also has its ER+ breast cancer drug candidate in Phase II stage of development. GlaxoSmithKline has one drug candidate in Phase I stage of development. However, the development of two of the ER+ breast cancer drug candidate of Novartis Pharmaceuticals Corporation was found to be inactive.
Some of the key players developing drugs for ER+ breast cancer includes Chipscreen Biosciences, Ltd., Eli Lilly & Company, Genentech, Inc., Novartis AG, Ipsen, Syndax Pharmaceuticals, Inc., Tesaro, Inc Astellas Pharma Inc., AstraZeneca plc, and Bayer AG.
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