Combining Emerging Agents in Advanced Breast Cancer

Abstract

Newer treatments have improved survival for patients with metastatic breast cancer over the last two decades, and a battery of new cytotoxic and targeted therapies is continuing to enhance this trend. This review outlines recent data and ongoing research in this area, by highlighting new developments (regarding approved but relatively new classes of cytotoxic and targeted agents) and also new classes of targeted therapy that are undergoing clinical evaluation. Mechanisms for synergy between agents are discussed where data are available, as is information on the rationale behind the development of agents that inhibit angiogenesis, DNA repair, histone deacetylases, heat shock proteins, or various signaling pathways in tumor proliferation. The abundance of clinical research surrounding anticancer agents, together with ongoing cancer biology research, is expected to further increase the available pool of therapeutic options for metastatic breast cancer. Concomitantly, in the absence of an effective targeted monotherapy, a better understanding of the interplay between biologic and cytotoxic anticancer agents will improve our ability to rationally design combination regimens with better efficacy and tolerability. The Oncologist 2011;16:760 -771

Superior antimitogenic and chemosensitization activities of the combination treatment of the histone deacetylase inhibitor apicidin and proteasome inhibitors on human colorectal cancer cells

“…New combination therapies for cancer are expected to produce enhanced efficacy, improved selectivity, and reduced toxicity. An ideal combination regimen would consist of agents with different mechanisms of action, leading to complementary antitumor activities and little cross resistance (27). In the present study, exposure to submicromolar concentrations of APC in combination with submicromolar concentrations of MG132 and nanomolar concentrations of EPM or PI-1 synergistically decreased the survival of cancer cells when compared with the single treatments (Fig.…”

Transcutaneous carbon dioxide application suppresses bone destruction caused by breast cancer metastasis

“…Recent therapeutic strategies for treating bone metastasis include surgery, radiotherapy and osteoclast inhibitors, such as bisphosphonates and denosumab, the human monoclonal antibody used to neutralize RANKL. Regardless of the wide use of these treatments, radiotherapy should still be administered for symptom palliation (57), although bisphosphonates and denosumab can cause unfavorable side-effects, such as osteonecrosis of the jaw (11)(12)(13)(14). Based on these findings, new strategies for the treatment of bone metastases with fewer side-effects are required.…”

“…However, the effects of these treatment modalities remain limited. In addition, osteonecrosis of the jaw and hypocalcemia represent serious side-effects and long-term prognosis associated with these treatments remains unknown (11)(12)(13)(14).…”

Patient Case Lessons: Endocrine Management of Advanced Breast Cancer

“…Advances in endocrine-based therapeutics have improved survival for women with HR þ ABC. [10][11][12][13] And because women with HR þ breast cancer are living longer, patient quality of life has come to the forefront of clinical decision-making. 12 The following includes several factors that should be considered when selecting from among available therapies for women with HR þ ABC.…”