Anti-cancer mechanisms of the most used drugs worldwide: old drugs, new insights

Abstract

Despite recent therapeutical improvements, cancer remains the second leading cause of death. Therefore there is an emerging need for novel cancer treatments. Development of novel anti-cancer drugs to fulfill the need for novel treatments is expensive, takes a long time and goes along with a low change of gaining marketing authorization. An alternative cheaper and faster approach to fulfil the need of new anti-cancer drugs is drug repurposing. The worldwide most used drugs could be potential candidates for drug repurposing since their intensive use provides extensive safety data. Therefore, mechanisms that clarify anti-cancer activity of eight of the most used drugs worldwide and the drug classes where they belong to were investigated in this study. Literature review showed that the drug gabapentin and the drug classes statins, renin angiotensin system (RAS) inhibitors, selective betablockers (BBs), dihydropyridine calcium channel blockers (CCBs), biguanides and protein pump inhibitors (PPIs) showed potential anti-tumorigenic effects in vitro and in vivo. The anti-cancer effects were established by targeting of several cancer hallmarks including: sustaining proliferation, induction of invasion and metastasis, avoiding immune destruction, induction of angiogenesis, deregulation of cellular energetics, genome instability and resisting cell death. Beside the drug effects on cancer hallmarks, it was shown that some drugs induced the delivery of chemotherapeutic drugs. In addition, the drug classes statins, RAS inhibitors, selective BBs, biguanides and PPIs showed combinational effects with conventional anti-cancer drugs, which increases the changes of successful drug repurposing since drugs have higher changes to get authorized as repurposed drugs if they will be combined. Overall, anti-cancer mechanisms were identified for all the investigated drugs. These mechanisms support suggested anti-cancer activity of the investigated drugs and therefore it was concluded that the drug gabapentin and the drug classes statins, RAS inhibitors, selective betablockers, dihydropyridine CCBs, biguanides and PPIs have the potential to be used for cancer drug repurposing. Since the drug classes statins, RAS inhibitors, selective BBs, biguanides and PPIs showed combinational effects with conventional treatments, these drug classes were especially considered as potential agents for cancer drug repurposing.