The phosphatidylinositol 3 kinase （PI3K）/AKT pathway is genetically targeted in more pathway components and in more tumor types than any other growth factor signaling pathway, and thus is frequently activated as a c...The phosphatidylinositol 3 kinase （PI3K）/AKT pathway is genetically targeted in more pathway components and in more tumor types than any other growth factor signaling pathway, and thus is frequently activated as a cancer driver. More importantly, the PI3K/AKT pathway is composed of multiple bifurcating and converging kinase cascades, providing many potential targets for cancer therapy. Renal cell carcinoma （RCC） is a high-risk and high-mortality cancer that is notoriously resistant to traditional chemotherapies or radiotherapies. The PI3K/AKT pathway is modestly mutated but highly activated in RCC, representing a promising drug target. Indeed, PI3K pathway inhibitors of the rapalog family are approved for use in RCC. Recent large-scale integrated analyses of a large number of patients have provided a molecular basis for RCC, reiterating the critical role of the PI3K/AKT pathway in this cancer. In this review, we summarize the genetic alterations of the PI3K/AKT pathway in RCC as indicated in the latest large-scale genome sequencing data, as well as treatments for RCC that target the aberrant activated PI3K/AKT pathway.展开更多
结直肠癌是全球发病率第三的恶性肿瘤。目前晚期结直肠癌的治疗以化疗为基石。2021年美国临床肿瘤学会(American Society of Clinical Oncology,ASCO)及欧洲肿瘤内科学(European Society of Medical Oncology,ESMO)公布了多项晚期结直...结直肠癌是全球发病率第三的恶性肿瘤。目前晚期结直肠癌的治疗以化疗为基石。2021年美国临床肿瘤学会(American Society of Clinical Oncology,ASCO)及欧洲肿瘤内科学(European Society of Medical Oncology,ESMO)公布了多项晚期结直肠癌免疫及靶向治疗研究进展。在免疫治疗领域,首先,对于微卫星高度不稳定(microsatellite instability-high,MSI-H)的晚期结直肠癌,KEYNOTE-177研究奠定了帕博利珠单抗一线治疗的地位,并改写中国临床肿瘤学会(Chinese Society of Clinical Oncology,CSCO)结直肠癌诊疗指南;其次,免疫联合化疗±靶向药物一线治疗微卫星稳定(microsatellite stability,MSS)患者极具潜力,有望更进一步改善MSS人群的预后;第三,免疫联合抗血管药物后线治疗MSS患者有了新的佐证,Ⅲ期临床研究计日以俟。在靶向治疗领域,V-Ki-ras2 Kirsten大鼠肉瘤病毒癌基因同源物(V-Ki-ras 2 Kirsten rat sarcoma viral oncogene homolog,KRAS) G12C突变晚期结直肠癌迎来新突破,adagrasib单药或联合西妥昔单抗可大幅提升预后;对于V-raf鼠肉瘤病毒癌基因同源体B(V-raf murine sarcoma viral oncogene homolog,BRAF) V600E突变患者,FIRE-4.5研究也进一步奠定贝伐珠单抗联合FOLFOXIRI三药化疗方案(氟尿嘧啶/亚叶酸钙+奥沙利铂+伊立替康)的一线治疗地位。本文就2021年国内外有关晚期结直肠癌的治疗研究进展作整理报告。展开更多
基金supported by the grant from The University of Texas MD Anderson Cancer Center Kidney Cancer Multidisciplinary Research Program to ZDthe NCI CCSG grant(No. P30 CA016672)the GDAC grant(No.5U24CA143883)
文摘The phosphatidylinositol 3 kinase （PI3K）/AKT pathway is genetically targeted in more pathway components and in more tumor types than any other growth factor signaling pathway, and thus is frequently activated as a cancer driver. More importantly, the PI3K/AKT pathway is composed of multiple bifurcating and converging kinase cascades, providing many potential targets for cancer therapy. Renal cell carcinoma （RCC） is a high-risk and high-mortality cancer that is notoriously resistant to traditional chemotherapies or radiotherapies. The PI3K/AKT pathway is modestly mutated but highly activated in RCC, representing a promising drug target. Indeed, PI3K pathway inhibitors of the rapalog family are approved for use in RCC. Recent large-scale integrated analyses of a large number of patients have provided a molecular basis for RCC, reiterating the critical role of the PI3K/AKT pathway in this cancer. In this review, we summarize the genetic alterations of the PI3K/AKT pathway in RCC as indicated in the latest large-scale genome sequencing data, as well as treatments for RCC that target the aberrant activated PI3K/AKT pathway.
文摘结直肠癌是全球发病率第三的恶性肿瘤。目前晚期结直肠癌的治疗以化疗为基石。2021年美国临床肿瘤学会(American Society of Clinical Oncology,ASCO)及欧洲肿瘤内科学(European Society of Medical Oncology,ESMO)公布了多项晚期结直肠癌免疫及靶向治疗研究进展。在免疫治疗领域,首先,对于微卫星高度不稳定(microsatellite instability-high,MSI-H)的晚期结直肠癌,KEYNOTE-177研究奠定了帕博利珠单抗一线治疗的地位,并改写中国临床肿瘤学会(Chinese Society of Clinical Oncology,CSCO)结直肠癌诊疗指南;其次,免疫联合化疗±靶向药物一线治疗微卫星稳定(microsatellite stability,MSS)患者极具潜力,有望更进一步改善MSS人群的预后;第三,免疫联合抗血管药物后线治疗MSS患者有了新的佐证,Ⅲ期临床研究计日以俟。在靶向治疗领域,V-Ki-ras2 Kirsten大鼠肉瘤病毒癌基因同源物(V-Ki-ras 2 Kirsten rat sarcoma viral oncogene homolog,KRAS) G12C突变晚期结直肠癌迎来新突破,adagrasib单药或联合西妥昔单抗可大幅提升预后;对于V-raf鼠肉瘤病毒癌基因同源体B(V-raf murine sarcoma viral oncogene homolog,BRAF) V600E突变患者,FIRE-4.5研究也进一步奠定贝伐珠单抗联合FOLFOXIRI三药化疗方案(氟尿嘧啶/亚叶酸钙+奥沙利铂+伊立替康)的一线治疗地位。本文就2021年国内外有关晚期结直肠癌的治疗研究进展作整理报告。
