Abramson Cancer Center, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Int J Mol Sci. 2021 Nov 17;22(22):12402. doi: 10.3390/ijms222212402.
(rat sarcoma virus) mutant cancers remain difficult to treat despite the advances in targeted therapy and immunotherapy. Targeted therapies against the components of mitogen-activated protein kinase (MAPK) pathways, including , RAF, MEK, and ERK, have demonstrated activity in mutant and, in limited cases, mutant cancer. mutant cancers have been found to activate adaptive resistance mechanisms such as autophagy during MAPK inhibition. Here, we review the recent clinically relevant advances in the development of the MAPK pathway and autophagy inhibitors and focus on their application to mutant cancers. We provide analysis of the preclinical rationale for combining the MAPK pathway and autophagy and highlight the most recent clinical trials that have been launched to capitalize on this potentially synthetic lethal approach to cancer therapy.
（大鼠肉瘤病毒）突变癌症尽管在靶向治疗和免疫治疗方面取得了进展，但仍然难以治疗。针对丝裂原活化蛋白激酶（MAPK）途径成分的靶向治疗，包括 RAF、MEK 和 ERK，已在 突变和在有限的情况下， 突变癌症中显示出活性。已经发现 突变癌症在 MAPK 抑制期间通过自噬激活适应性耐药机制。在这里，我们回顾了 MAPK 途径和自噬抑制剂在开发方面的最新临床相关进展，并重点介绍了它们在 突变癌症中的应用。我们对组合 MAPK 途径和自噬的临床前原理进行了分析，并强调了最近启动的临床试验，以利用这种潜在的合成致死方法治疗癌症。
