Guerriero Ilaria, Monaco Gianni, Coppola Vincenzo, Orlacchio Arturo
Biogem Institute for Genetic Research Gaetano Salvatore, Ariano Irpino, 83031 Avellino, Italy.
Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
Pharmaceuticals (Basel). 2020 Nov 22;13(11):413. doi: 10.3390/ph13110413.
Non-small cell lung cancer (NSCLC) remains the most prevalent and one of the deadliest cancers worldwide. Despite recent success, there is still an urgent need for new therapeutic strategies. It is also becoming increasingly evident that combinatorial approaches are more effective than single modality treatments. This review proposes that the serum and glucocorticoid-inducible kinase 1 (SGK1) may represent an attractive target for therapy of NSCLC. Although ubiquitously expressed, SGK1 deletion in mice causes only mild defects of ion physiology. The frequent overexpression of SGK1 in tumors is likely stress-induced and provides a therapeutic window to spare normal tissues. SGK1 appears to promote oncogenic signaling aimed at preserving the survival and fitness of cancer cells. Most importantly, recent investigations have revealed the ability of SGK1 to skew immune-cell differentiation toward pro-tumorigenic phenotypes. Future studies are needed to fully evaluate the potential of SGK1 as a therapeutic target in combinatorial treatments of NSCLC. However, based on what is currently known, SGK1 inactivation can result in anti-oncogenic effects both on tumor cells and on the immune microenvironment. A first generation of small molecules to inactivate SGK1 has already been already produced.
非小细胞肺癌（NSCLC）仍然是全球最常见且最致命的癌症之一。尽管近期取得了成功，但仍迫切需要新的治疗策略。越来越明显的是，联合治疗方法比单一治疗方式更有效。本综述提出，血清和糖皮质激素诱导激酶1（SGK1）可能是NSCLC治疗的一个有吸引力的靶点。尽管SGK1在全身广泛表达，但小鼠体内SGK1基因缺失仅导致离子生理学的轻微缺陷。肿瘤中SGK1的频繁过表达可能是由应激诱导的，这为保护正常组织提供了一个治疗窗口。SGK1似乎促进了旨在维持癌细胞存活和适应性的致癌信号传导。最重要的是，最近的研究揭示了SGK1能够使免疫细胞分化偏向促肿瘤表型。需要进一步的研究来全面评估SGK1作为NSCLC联合治疗靶点的潜力。然而，基于目前已知的情况，SGK1失活可对肿瘤细胞和免疫微环境产生抗癌作用。已经产生了第一代使SGK1失活的小分子。
