Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43/6, 2650, Edegem, Belgium.
Integrated Personalized and Precision Oncology Network (IPPON), Center for Oncological Research (CORE), University of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610, Wilrijk, Belgium.
Curr Treat Options Oncol. 2023 Aug;24(8):965-987. doi: 10.1007/s11864-023-01095-y. Epub 2023 May 22.
One of the great challenges in digestive oncology is choosing the optimal therapy for RAS-mutated metastatic colorectal cancer (mCRC). Even though the RAS genes and accompanying pathway were identified decades ago and extensive knowledge exists on their role in carcinogenesis, it has proven challenging to translate these insights into new therapies and clinical benefit for patients. However, recently, new drugs targeting this pathway (for example, KRAS inhibitors) have shown promising results in clinical trials, as monotherapy or in combination regimens. Although resistance remains an important issue, more knowledge on adaptive resistance and feedback loops in the RAS-pathway has led to strategical combination regimens to overcome this problem. In the past year, many encouraging results have been published or presented at conferences. Even though some of the data is still preliminary, these studies may bring practice-changing results and can lead to a clinical benefit for patients over the coming years. Because of these recent developments, the treatment of RAS-mutated mCRC has become a topic of great interest. Therefore, in this review, we will summarize the standard of care and discuss the most important emerging therapies for this patient population.
消化系统肿瘤学的一大挑战是为 RAS 突变转移性结直肠癌 (mCRC) 选择最佳治疗方法。尽管 RAS 基因及其相关通路几十年前就已被发现，并且人们对其在癌变中的作用有了广泛的了解，但将这些认识转化为新的治疗方法并为患者带来临床获益仍然具有挑战性。然而，最近，针对该通路的新药（例如，KRAS 抑制剂）在临床试验中作为单药或联合方案显示出了有前景的结果。尽管耐药性仍然是一个重要问题，但对 RAS 通路中的适应性耐药和反馈环的更多了解导致了策略性联合方案来克服这个问题。在过去的一年中，许多令人鼓舞的结果已经在会议上发表或展示。尽管一些数据仍然是初步的，但这些研究可能会带来改变实践的结果，并在未来几年为患者带来临床获益。由于这些新的发展，RAS 突变型 mCRC 的治疗已成为一个备受关注的话题。因此，在这篇综述中，我们将总结标准治疗方法，并讨论针对这一患者群体的最重要的新兴治疗方法。
