A multifaceted role of bisphosphonates from palliative care to anti-cancer therapy in solid tumors

Bisphosphonates (P-C-Ps) also called diphosphonates are the structural analogs of naturally occurring pyrophosphates. Bisphosphonates are traditionally used and shown to provide long-term success in the treatment and prevention of osteoporosis and other bone loss pathologies. Furthermore, bisphosphonates are gaining popularity in the present era of cancer therapeutics and prevention. The usage of bisphosphonates as adjuvant or neoadjuvant therapy, either as a single agent or combined with other chemotherapy, has been studied in different solid tumors. This review aims to present the various roles of bisphosphonates in solid tumors.

Articles in MEDLINE/PubMed and the National Institutes of Health Clinical Trials Registry (http://www. Clinicaltrials.gov) between 1 January 2011 and 1 February 2022 were extracted using MeSH terms "bisphosphonates/diphosphosphonates and mechanism," "bisphosphonates and breast cancer," "bisphosphonates and prostate cancer," "bisphosphonates and lung cancer," "bisphosphonates and cancer risk," and "bisphosphonates and adverse events." Manual searches of some major oncology journals were also conducted.

This review article focuses on the antitumor activity of bisphosphonates, safety profile, and the role of bisphosphonates as preventive, neoadjuvant, and adjuvant chemotherapy. A significant improvement in overall survival and cancer-specific survival and recurrence-free survival with the usage of bisphosphonates is noted in breast cancer patients, particularly in post-menopausal women. Though great progress has been achieved in over 20 years, further research is needed to identify the subgroup of patients that are most likely to benefit from adjuvant bisphosphonate therapy and to determine regimens with greater efficacy and better safety profile.