There is extensive in vitro and in vivo preclinical evidence that bisphosphonates, particularly zoledronic acid and ibandronate, have antitumor activity, can reduce skeletal tumor burden, and might potentially have antitumor activity outside the bone microenviroment. The authors of this review highlight the importance of correct sequencing of these compounds when used in conjunction with cytotoxic drugs, targeted molecular therapies, and radiotherapy. The need to identify new molecular targets of nitrogen-containing bisphosphonates is discussed in this context and the correct sequence and the timing of drug administration could help drive molecular research and determine the efficacy of the therapy, both in advanced disease and in the adjuvant setting.
- Daniele Santini
- Michele Caraglia
- Giuseppe Tonini
