Therapeutic implications of antiangiogenic agents and poly-adenosine diphosphate ribose polymerase (PARP) inhibitors in breast cancer: Current status and future perspectives

Abstract

Angiogenesis exhibits an integral role in cancer development and metastasis, therefore, antiangiogenic therapy forms the basis of several promising treatment strategies for breast cancer. Moreover, DNA damage has long been exploited in cancer chemotherapy and poly-adenosine diphosphate ribose polymerase (PARP) inhibitors constitute a novel group of drugs for the targeted disruption of DNA repair phenomenon attributed to breast cancer. Several antiangiogenic drugs and PARP inhibitors are effectively used as sole agents for the therapeutic management of early breast cancer and breast cancer gene mutation–induced breast cancer, respectively. Whereas, other antiangiogenic agents are employed for the ancillary therapy of metastatic breast cancer in conjunction with chemotherapeutic drugs. Likewise, some PARP inhibitors are recommended as adjuncts to chemotherapy against the triple-negative form of breast cancer. Combinations of PARP inhibitors with immunotherapy have also demonstrated favorable outcomes and offer an efficient treatment strategy for breast cancer. Currently, the combinations of antiangiogenic agents and PARP inhibitors are under investigation for prospective synergistic or additive effects in breast cancer. Despite being suggested for high-risk patients, the prophylactic use of PARP inhibitors has not been supported by means of preclinical or clinical studies. Finally, the identification of patient cohorts, determination of predictive biomarkers, optimization of dosing strategies, validation of long-term safety, and containment of resistance issues, necessitate proper attention for improving the clinical efficacy of potentially useful antiangiogenic agents and PARP inhibitors against breast cancer.