Farooq Hafsa, Bien Harold, Chang Victor, Becker Daniel, Park Yeun-Hee, Bates Susan E
Section of Hematology and Oncology, VA Northport Medical Center, Northport, NY; Division of Hematology and Oncology, Renaissance School of Medicine, Stony Brook, NY.
Section of Hematology and Oncology, VA Northport Medical Center, Northport, NY; Division of Hematology and Oncology, Renaissance School of Medicine, Stony Brook, NY.
Semin Oncol. 2022 Jun;49(3-4):319-325. doi: 10.1053/j.seminoncol.2022.06.008. Epub 2022 Jul 1.
Emerging evidence suggests that STK11 alterations, frequently found in non-small-cell lung cancers, may be prognostic and/or predictive of response to therapy, particularly immunotherapy. STK11 affects multiple important cellular pathways, and mutations lead to tumor growth by creating an immunosuppressive and altered metabolic environment through changes in AMPK, STING, and vascular endothelial growth factor pathways. We illustrate the questions surrounding STK11 genomic alteration in NSCLC with a case series comprising six United States Veterans from a single institution. We discuss the history of STK11, review studies on its clinical impact, and describe putative mechanisms of how loss of STK11 might engender resistance to immunotherapy or other therapies. While the exact impact of STK11 alteration in non-small-cell lung cancer remain to be fully elucidated, future research and ongoing clinical trials will help us better understand its role in cancer development and devise more effective treatment strategies.
新出现的证据表明,在非小细胞肺癌中经常发现的STK11改变可能具有预后意义和/或预测对治疗的反应,特别是免疫治疗。STK11影响多个重要的细胞通路,突变通过改变AMPK、STING和血管内皮生长因子通路,营造免疫抑制和代谢改变的环境,从而导致肿瘤生长。我们通过一个来自单一机构的六名美国退伍军人的病例系列,阐述了非小细胞肺癌中围绕STK11基因改变的问题。我们讨论了STK11的研究历史,回顾了关于其临床影响的研究,并描述了STK11缺失可能如何导致对免疫治疗或其他治疗产生耐药性的假定机制。虽然STK11改变在非小细胞肺癌中的确切影响仍有待充分阐明,但未来的研究和正在进行的临床试验将帮助我们更好地理解其在癌症发展中的作用,并制定更有效的治疗策略。