Troy B Schedin, Virginia F Borges, Elena Shagisultanova
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Overcoming Therapeutic Resistance of Triple Positive Breast Cancer with CDK4/6 Inhibition.
Triple positive breast cancers overexpress both the human epidermal growth factor receptor 2 (HER2) oncogene and the hormonal receptors (HR) to estrogen and progesterone. These cancers represent a unique therapeutic challenge because of a bidirectional cross-talk between the estrogen receptor alpha (ERα) and HER2 pathways leading to tumor progression and resistance to targeted therapy. Attempts to combine standard of care HER2-targeted drugs with antihormonal agents for the treatment of HR+/HER2+ breast cancer yielded encouraging results in preclinical experiments but did improve overall survival in clinical trial. In this review, we dissect multiple mechanisms of therapeutic resistance typical of HR+/HER2+ breast cancer, summarize prior clinical trials of targeted agents, and describe novel rational drug combinations that include antihormonal agents, HER2-targeted drugs, and CDK4/6 inhibitors for treatment of the HR+/HER2+ breast cancer subtype.
期刊介绍：
International Journal of Breast Cancer is a peer-reviewed, Open Access journal that provides a forum for scientists, clinicians, and health care professionals working in breast cancer research and management. The journal publishes original research articles, review articles, and clinical studies related to molecular pathology, genomics, genetic predisposition, screening and diagnosis, disease markers, drug sensitivity and resistance, as well as novel therapies, with a specific focus on molecular targeted agents and immune therapies.
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