The use of bisphosphonates and statins in cancer treatment in dogs: New therapeutic approaches

İngilizce (OpenAlex)

Statins and bisphosphonates are increasingly recognized for their anticancer potential, particularly due to their effects on the mevalonate pathway. Bisphosphonates exert their effects on tumor cells by inhibiting a key enzyme in this pathway, farnesyl diphosphate synthase, thereby preventing protein prenylation and the subsequent activation of intracellular signalling proteins such as Ras. Statins competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase, the major rate-limiting enzyme that controls the conversion of HMG-CoA to mevalonic acid. The sequential action of both drugs on complementary targets within the mevalonate-dependent cascade, where they hit the same critical metabolic pathway at two different points, provides a potent therapeutic rationale for their combined use to maximize the anticancer effect. This review aims to examine in vitro and in vivo studies regarding the use of statins and bisphosphonates based on their mechanisms of action, as well as the clinical expectations and the potential controversial aspects of this potential synergy in therapeutic applications in cancer treatment.