Cancer Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, Australia.
Cells. 2021 Mar 16;10(3):659. doi: 10.3390/cells10030659.
Molecular alterations in cancer genes and associated signaling pathways are used to inform new treatments for precision medicine in cancer. Small molecule inhibitors and monoclonal antibodies directed at relevant cancer-related proteins have been instrumental in delivering successful treatments of some blood malignancies (e.g., imatinib with chronic myelogenous leukemia (CML)) and solid tumors (e.g., tamoxifen with ER positive breast cancer and trastuzumab for HER2-positive breast cancer). However, inherent limitations such as drug toxicity, as well as acquisition of de novo or acquired mechanisms of resistance, still cause treatment failure. Here we provide an up-to-date review of the successes and limitations of current targeted therapies for cancer treatment and highlight how recent technological advances have provided a new level of understanding of the molecular complexity underpinning resistance to cancer therapies. We also raise three basic questions concerning cancer drug discovery based on molecular markers and alterations of selected signaling pathways, and further discuss how combination therapies may become the preferable approach over monotherapy for cancer treatments. Finally, we consider novel therapeutic developments that may complement drug delivery and significantly improve clinical response and outcomes of cancer patients.
癌症基因和相关信号通路的分子改变被用于为癌症的精准医学提供新的治疗方法。针对相关癌症相关蛋白的小分子抑制剂和单克隆抗体在提供某些血液恶性肿瘤（例如慢性髓性白血病（CML）的伊马替尼）和实体瘤（例如 ER 阳性乳腺癌的他莫昔芬和 HER2 阳性乳腺癌的曲妥珠单抗）的成功治疗方面发挥了重要作用。然而，药物毒性等固有局限性以及新出现或获得的耐药机制仍然导致治疗失败。在这里，我们提供了对癌症治疗当前靶向治疗成功和局限性的最新综述，并强调了最近的技术进步如何为理解癌症治疗耐药性的分子复杂性提供了新的水平。我们还基于分子标记物和选定信号通路的改变提出了关于癌症药物发现的三个基本问题，并进一步讨论了联合治疗如何可能成为癌症治疗的首选方法，而不是单一疗法。最后，我们考虑了可能补充药物输送并显著改善癌症患者临床反应和结果的新型治疗方法的发展。
