BRAF 突变型转移性结肠癌中免疫治疗作用的叙述性综述
A Narrative Review of the Role of Immunotherapy in Metastatic Carcinoma of the Colon Harboring a BRAF Mutation.
作者信息
Colombo Alfredo, Concetta Porretto Maria, Gebbia Vittorio, Sambataro Daniela, Scandurra Giuseppina, Valerio Maria Rosaria
机构信息
Medical Oncology Unit, CdC Macchiarella, Palermo, Italy.
Medical Oncology, Department of Medicine and Surgery, Kore University of Enna, Enna, Italy;
出版信息
In Vivo. 2025 Jan-Feb;39(1):25-36. doi: 10.21873/invivo.13802.
Patients affected by metastatic carcinoma of the colon/rectum (mCRC) harboring mutations in the BRAF gene (MBRAF) respond poorly to conventional therapy and have a prognosis worse than that of patients without mutations. Despite the promising outcomes of targeted therapy utilizing multi-targeted inhibition of the mitogen-activated protein kinase (MAPK) signaling system, the therapeutic efficacy, especially for the microsatellite stable/DNA proficient mismatch repair (MSS/PMMR) subtype, remains inadequate. Patients with MBRAF/mCRC and high microsatellite instability or DNA deficient mismatch repair (MSI-H/DMMR) exhibit a substantial tumor mutation burden, suggesting a high probability of response to immunotherapy. It is widely acknowledged that MSS/pMMR/mCRC is an immunologically "cold" malignancy that exhibits resistance to immunotherapy. The integration of targeted therapy and immunotherapy may enhance clinical outcomes in patients with MBRAF/mCRC. Efforts to enhance outcomes are exclusively focused on MSS/DMMR-BRAF mutant cancers, which constitute the largest proportion. This review evaluates the clinical efficacy and advancement of novel immune checkpoint blockade therapies for MSI-H/DMMR and MSS/PMMR BRAF mutant mCRC. We examine potential indicators in the tumor immune milieu for forecasting immunotherapeutic response in BRAF mutant mCRC.
患有结肠/直肠癌转移癌(mCRC)且BRAF基因发生突变(MBRAF)的患者对传统疗法反应不佳,预后比未发生突变的患者更差。尽管利用丝裂原活化蛋白激酶(MAPK)信号系统的多靶点抑制进行靶向治疗取得了令人鼓舞的成果,但治疗效果,尤其是对微卫星稳定/DNA错配修复功能正常(MSS/PMMR)亚型的治疗效果,仍然不尽人意。MBRAF/mCRC且微卫星高度不稳定或DNA错配修复缺陷(MSI-H/DMMR)的患者表现出大量肿瘤突变负荷,提示对免疫治疗有较高的反应概率。众所周知,MSS/pMMR/mCRC是一种免疫“冷”恶性肿瘤,对免疫治疗表现出抗性。靶向治疗与免疫治疗的联合应用可能会改善MBRAF/mCRC患者的临床结局。改善结局的努力主要集中在占比最大的MSS/DMMR-BRAF突变癌症上。本综述评估了新型免疫检查点阻断疗法对MSI-H/DMMR和MSS/PMMR BRAF突变mCRC的临床疗效及进展情况。我们研究了肿瘤免疫微环境中预测BRAF突变mCRC免疫治疗反应的潜在指标。