Kirsten Rat Sarcoma ( KRAS ) gene somatic point mutations is one of the most prominently mutated proto-oncogenes known to date, and accounts for approximately 60% of all colorectal cancer cases. One of the most exciting drug development areas against colorectal cancer is the targeting of undruggable kinases and kinase-substrate molecules, although whether and how they can be integrated with other therapies remains a question. Current clinical trial data have provided supporting evidence on the use of combination treatment involving MEK inhibitors and either one of the PI3K inhibitors for patients with metastatic colorectal cancer to avoid the development of resistance and provide effective therapeutic outcome rather than using a single agent alone. Many clinical trials are also ongoing to evaluate different combinations of these pathway inhibitors in combination with immunotherapy for patients with colorectal cancer whose current palliative treatment options are limited. Nevertheless, continued assessment of these targeted cancer therapies will eventually allow patients with colorectal cancer to be treated using a personalized medicine approach. In this review, the most recent scientific approaches and clinical trials targeting KRAS mutations directly or indirectly for the management of colorectal cancer are discussed.

中文翻译：

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结直肠癌 KRAS 靶向治疗的当前进展和趋势

克尔斯滕大鼠肉瘤 (KRAS) 基因体细胞点突变是迄今为止已知的最显着突变的原癌基因之一，约占所有结直肠癌病例的 60%。针对结直肠癌最令人兴奋的药物开发领域之一是靶向不可药化的激酶和激酶底物分子，尽管它们是否以及如何与其他疗法整合仍然是一个问题。目前的临床试验数据为转移性结直肠癌患者使用涉及 MEK 抑制剂和其中一种 PI3K 抑制剂的联合治疗提供了支持证据，以避免产生耐药性并提供有效的治疗结果，而不是单独使用单一药物。许多临床试验也正在进行中，以评估这些通路抑制剂的不同组合与免疫疗法相结合，用于目前姑息治疗选择有限的结直肠癌患者。尽管如此，对这些靶向癌症疗法的持续评估最终将使结直肠癌患者能够使用个性化医疗方法进行治疗。在这篇综述中，讨论了直接或间接针对 KRAS 突变治疗结直肠癌的最新科学方法和临床试验。对这些靶向癌症疗法的持续评估最终将使结直肠癌患者能够使用个性化医疗方法进行治疗。在这篇综述中，讨论了直接或间接针对 KRAS 突变治疗结直肠癌的最新科学方法和临床试验。对这些靶向癌症疗法的持续评估最终将使结直肠癌患者能够使用个性化医疗方法进行治疗。在这篇综述中，讨论了直接或间接针对 KRAS 突变治疗结直肠癌的最新科学方法和临床试验。