The management of metastatic colorectal cancer in patients harboring RAS mutations primarily involves chemotherapy, often combined with bevacizumab, as a standard first-line treatment. However, emerging evidence suggests that tumors in a subset of these patients may experience a conversion from RAS-mutant status to RAS wild type (wt) during or after chemotherapy, a process referred to as “RAS conversion” or “neo-RAS wt”. Understanding the mechanisms driving the neo-RAS wt phenomenon is crucial for its application in personalized medicine. Hypotheses suggest that selective pressure from chemotherapy may lead to a decrease in the number of mutant RAS clones or an outgrowth of pre-existing RAS wt clones. Further research is needed to validate these mechanisms and understand the impact of the neo-RAS wt phenomenon on long-term outcomes, such as overall survival and progression-free survival. This review provides a comprehensive overview of the current understanding of the neo-RAS wt phenomenon, including its incidence, potential mechanisms, and clinical implications.
对于携带RAS突变的转移性结直肠癌患者，其治疗主要采用化疗联合贝伐珠单抗作为标准一线方案。然而，新近证据表明，部分患者在化疗期间或治疗后可能出现肿瘤从RAS突变状态转变为RAS野生型（wt）的现象，这一过程被称为“RAS转化”或“新发RAS野生型”。理解驱动新发RAS野生型现象的机制对于其在个体化医疗中的应用至关重要。现有假说认为，化疗的选择性压力可能导致突变RAS克隆数量减少或预先存在的RAS野生型克隆扩增。未来需要进一步研究验证这些机制，并明确新发RAS野生型现象对总生存期和无进展生存期等长期预后的影响。本综述系统阐述了当前对新发RAS野生型现象的认识，包括其发生率、潜在机制及临床意义。
肿瘤(癌症)患者之家