Bayat Mokhtari Reza, Homayouni Tina S, Baluch Narges, Morgatskaya Evgeniya, Kumar Sushil, Das Bikul, Yeger Herman
Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Paediatric Laboratory Medicine, The Hospital for Sick Children and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Oncotarget. 2017 Jun 6;8(23):38022-38043. doi: 10.18632/oncotarget.16723.
Combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anti-cancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner. This approach potentially reduces drug resistance, while simultaneously providing therapeutic anti-cancer benefits, such as reducing tumour growth and metastatic potential, arresting mitotically active cells, reducing cancer stem cell populations, and inducing apoptosis. The 5-year survival rates for most metastatic cancers are still quite low, and the process of developing a new anti-cancer drug is costly and extremely time-consuming. Therefore, new strategies that target the survival pathways that provide efficient and effective results at an affordable cost are being considered. One such approach incorporates repurposing therapeutic agents initially used for the treatment of different diseases other than cancer. This approach is effective primarily when the FDA-approved agent targets similar pathways found in cancer. Because one of the drugs used in combination therapy is already FDA-approved, overall costs of combination therapy research are reduced. This increases cost efficiency of therapy, thereby benefiting the "medically underserved". In addition, an approach that combines repurposed pharmaceutical agents with other therapeutics has shown promising results in mitigating tumour burden. In this systematic review, we discuss important pathways commonly targeted in cancer therapy. Furthermore, we also review important repurposed or primary anti-cancer agents that have gained popularity in clinical trials and research since 2012.
联合治疗是一种将两种或更多治疗药物结合使用的治疗方式，是癌症治疗的基石。与单一疗法相比，抗癌药物的联合使用能提高疗效，因为它以典型的协同或相加方式作用于关键通路。这种方法有可能降低耐药性，同时带来抗癌治疗益处，如减少肿瘤生长和转移潜能、使有丝分裂活跃细胞停滞、减少癌症干细胞数量以及诱导细胞凋亡。大多数转移性癌症的5年生存率仍然很低，而且开发一种新的抗癌药物成本高昂且极为耗时。因此，人们正在考虑采用新策略来靶向那些能以可承受的成本提供高效结果的生存通路。一种这样的方法是重新利用最初用于治疗癌症以外其他疾病的治疗药物。当美国食品药品监督管理局（FDA）批准的药物靶向癌症中发现的类似通路时，这种方法尤其有效。由于联合治疗中使用的一种药物已经获得FDA批准，联合治疗研究的总体成本得以降低。这提高了治疗的成本效益，从而使“医疗服务不足者”受益。此外，将重新利用的药物与其他疗法相结合的方法在减轻肿瘤负担方面已显示出有前景的结果。在本系统评价中，我们讨论了癌症治疗中常见的重要靶向通路。此外，我们还综述了自2012年以来在临床试验和研究中受到关注的重要的重新利用或主要的抗癌药物。
