Treating Breast Cancer in the 21st Century: Emerging Biological Therapies

Abstract

For many years, the medical treatment of breast cancer was reliant solely on cytotoxic chemotherapy. However, over the past twenty years, treatment has evolved to a more target-directed approach. We now employ tailored therapy based on the presence or absence of receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER2). We expect this trend to continue, as agents that use novel approaches to target HER2, as well as targeting different portions of the HER signaling pathway, are in various stages of development. Notably, pertuzumab, a humanized monoclonal antibody that binds to a different domain of the extracellular portion of the HER2 receptor than trastuzumab, was recently approved for use, as was lapatinib, a small-molecule tyrosine kinase inhibitor. Patients with triple negative breast cancer, particularly those with the BRCA mutation, have more limited treatment options and carry a worse prognosis than those who are hormone receptor positive. However, recent data has shown that PARP inhibitors may have significant anti-tumor effect in those with this subtype of breast cancer. Novel agents that inhibit mTOR, PI3K, the insulin-like growth factor, heat shock protein 90, and histone deacetylase have shown promise in phase I-III trials and offer exciting new possibilities for the treatment of this often fatal disease. As we are presented with an ever increasing number of treatment options, the timing and combinations of therapeutic agents used becomes ever more complex in the age of personalized care, but we are hopeful that ultimately this will lead to improved patient outcomes.

Adjuvant chemotherapy in breast cancer: To use or not to use, the anthracyclines

“…Currently such novel agents, such as VEGF (vascular endothelial growth factor), PARP (poly ADP ribose polymerase), mTOR (mammalian target of rapamycin) and HDAC (histone deacetylase) inhibitors, are being studied in the neo-adjuvant, adjuvant and metastatic setting, along with anthracycline and nonanthracycline containing regimens [51] . These clinical trials will provide information on whether they can improve the outcome of patients with breast cancer and their interaction with the different standard chemotherapy agents.…”

Quercetin induces apoptosis and necroptosis in MCF-7 breast cancer cells

“…The best lines of defense, radiation therapy and chemotherapy, are unsatisfactory due to the untoward side effects on healthy cells and the problem of drug resistance (1). Searching for new compounds for the treatment of cancer is the aim of numerous studies, and many works are focused on plant-derived compounds that have curative potential.…”

Novel thiosemicarbazides induced apoptosis in human MCF-7 breast cancer cells via JNK signaling

“…About 6% of patients with newly diagnosed disease present with advanced or metastatic breast cancer (MBC) at the time of initial diagnosis, while about 40% of patients with early stage disease will subsequently develop metastasis. Despite the many advances in therapeutic regimens, MBC remains incurable, with an estimated 5-year overall survival rate of only 23% 6 . Resistance to chemotherapy is also a major problem in the management of breast cancer, where many of the initially responsive tumors relapse and develop resistance to diverse chemotherapeutic agents 7 .…”