Tilija Pun Nirmala, Jeong Chul-Ho
College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Daegu 42601, Korea.
Pharmaceuticals (Basel). 2021 May 16;14(5):470. doi: 10.3390/ph14050470.
Cancer is incurable because progressive phenotypic and genotypic changes in cancer cells lead to resistance and recurrence. This indicates the need for the development of new drugs or alternative therapeutic strategies. The impediments associated with new drug discovery have necessitated drug repurposing (i.e., the use of old drugs for new therapeutic indications), which is an economical, safe, and efficacious approach as it is emerged from clinical drug development or may even be marketed with a well-established safety profile and optimal dosing. Statins are inhibitors of HMG-CoA reductase in cholesterol biosynthesis and are used in the treatment of hypercholesterolemia, atherosclerosis, and obesity. As cholesterol is linked to the initiation and progression of cancer, statins have been extensively used in cancer therapy with a concept of drug repurposing. Many studies including in vitro and in vivo have shown that statin has been used as monotherapy to inhibit cancer cell proliferation and induce apoptosis. Moreover, it has been used as a combination therapy to mediate synergistic action to overcome anti-cancer drug resistance as well. In this review, the recent explorations are done in vitro, in vivo, and clinical trials to address the action of statin either single or in combination with anti-cancer drugs to improve the chemotherapy of the cancers were discussed. Here, we discussed the emergence of statin as a lipid-lowering drug; its use to inhibit cancer cell proliferation and induction of apoptosis as a monotherapy; and its use in combination with anti-cancer drugs for its synergistic action to overcome anti-cancer drug resistance. Furthermore, we discuss the clinical trials of statins and the current possibilities and limitations of preclinical and clinical investigations.
癌症无法治愈，因为癌细胞中不断进展的表型和基因型变化会导致耐药性和复发。这表明需要研发新药或采用替代治疗策略。与新药研发相关的障碍使得药物重新利用（即使用旧药用于新的治疗适应症）成为必要，这是一种经济、安全且有效的方法，因为它源于临床药物开发，甚至可能以已确立的安全概况和最佳剂量上市。他汀类药物是胆固醇生物合成中HMG-CoA还原酶的抑制剂，用于治疗高胆固醇血症、动脉粥样硬化和肥胖症。由于胆固醇与癌症的发生和发展有关，他汀类药物已被广泛用于癌症治疗，采用了药物重新利用的概念。许多包括体外和体内研究在内的研究表明，他汀类药物已被用作单一疗法来抑制癌细胞增殖并诱导凋亡。此外，它还被用作联合疗法来介导协同作用以克服抗癌药物耐药性。在这篇综述中，讨论了最近在体外、体内和临床试验中进行的探索，以探讨他汀类药物单独或与抗癌药物联合使用以改善癌症化疗的作用。在此，我们讨论了他汀类药物作为降脂药物的出现；其作为单一疗法抑制癌细胞增殖和诱导凋亡的用途；以及其与抗癌药物联合使用以发挥协同作用克服抗癌药物耐药性的用途。此外，我们还讨论了他汀类药物的临床试验以及临床前和临床研究的当前可能性和局限性。
