Gmeiner William H
Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Cancers (Basel). 2024 Mar 2;16(5):1029. doi: 10.3390/cancers16051029.
Colorectal cancer (CRC) is the second-leading cause of cancer-related mortality worldwide. CRC mortality results almost exclusively from metastatic disease (mCRC) for which systemic chemotherapy is often a preferred therapeutic option. Biomarker-based stratification of mCRC enables the use of precision therapy based on individual tumor mutational profiles. Activating mutations in the RAS/RAF/MAPK pathway downstream of EGFR signaling have, until recently, limited the use of EGFR-targeted therapies for mCRC; however, the development of anti-RAS and anti-RAF therapies together with improved strategies to limit compensatory signaling pathways is resulting in improved survival rates in several highly lethal mCRC sub-types (e.g., BRAF-mutant). The use of fluoropyrimidine (FP)-based chemotherapy regimens to treat mCRC continues to evolve contributing to improved long-term survival. Future advances in chemotherapy for mCRC will need to position development relative to the advances made in precision oncology.
结直肠癌（CRC）是全球癌症相关死亡的第二大原因。CRC死亡几乎完全由转移性疾病（mCRC）导致，对于mCRC，全身化疗通常是首选的治疗选择。基于生物标志物的mCRC分层使得能够根据个体肿瘤突变谱使用精准治疗。直到最近，表皮生长因子受体（EGFR）信号下游的RAS/RAF/丝裂原活化蛋白激酶（MAPK）途径中的激活突变限制了EGFR靶向疗法在mCRC中的应用；然而，抗RAS和抗RAF疗法的发展以及限制代偿性信号通路的改进策略，正在提高几种高致死性mCRC亚型（如BRAF突变型）的生存率。使用基于氟嘧啶（FP）的化疗方案治疗mCRC仍在不断发展，有助于提高长期生存率。mCRC化疗的未来进展需要相对于精准肿瘤学的进展来定位发展。
