PDF(Pubmed)
Abstract：
The cancer stem cell (SC) theory proposes that a population of SCs serves as the driving force behind fundamental tumor processes, including metastasis, recurrence, and resistance to therapy. The standard of care for patients with stage III and high-risk stage II colorectal cancer (CRC) includes surgery and adjuvant chemotherapy. Fluoropyrimidines and their combination with oxaliplatin increased the cure rates, being able to eradicate the occult metastatic SC in a fraction of patients. The treatment for unresectable metastatic CRC is based on chemotherapy, antibodies to VEGF and EGFR, and tyrosine-kinase inhibitors. Immunotherapy is used in MSI-H tumors. Currently used drugs target dividing cells and, while often effective at debulking tumor mass, these agents have largely failed to cure metastatic disease. SCs are generated either due to genetic and epigenetic alterations in stem/progenitor cells or to the dedifferentiation of somatic cells where diverse signaling pathways such as Wnt/β-catenin, Hedgehog, Notch, TGF-β/SMAD, PI3K/Akt/mTOR, NF-κB, JAK/STAT, DNA damage response, and Hippo-YAP play a key role. Anti-neoplastic treatments could be improved by elimination of SCs, becoming an attractive target for the design of novel agents. Here, we present a review of clinical trials assessing the efficacy of targeted treatment focusing on these pathways in CRC.
摘要：
癌症干细胞（SC）理论提出，SCs群体作为基本肿瘤过程背后的驱动力，包括转移,复发,和对治疗的抵抗力。III期和高危II期结直肠癌（CRC）患者的护理标准包括手术和辅助化疗。氟嘧啶类药物及其与奥沙利铂的联合使用可提高治愈率，能够根除一小部分患者的隐匿性转移性SC。不可切除的转移性CRC的治疗基于化疗，VEGF和EGFR抗体，和酪氨酸激酶抑制剂。免疫疗法用于MSI-H肿瘤。目前使用的药物靶向分裂细胞，虽然通常能有效缩小肿瘤肿块，这些药物在很大程度上未能治愈转移性疾病。SCs的产生是由于干细胞/祖细胞的遗传和表观遗传改变或体细胞的去分化，其中不同的信号通路如Wnt/β-catenin，刺猬,缺口,TGF-β/SMAD,PI3K/Akt/mTOR,NF-κB,JAK/STAT,DNA损伤反应,河马YAP发挥了关键作用。抗肿瘤治疗可以通过消除SCs来改善，成为设计新型制剂的有吸引力的目标。这里,我们综述了以这些途径为重点的靶向治疗在CRC中的疗效评估的临床试验.
