Larribère Lionel, Utikal Jochen
Skin Cancer Unit, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany.
Cancers (Basel). 2020 Jun 10;12(6):1524. doi: 10.3390/cancers12061524.
Tumorigenesis is correlated with abnormal expression and activity of G protein-coupled receptors (GPCRs) and associated G proteins. Oncogenic mutations in both GPCRs and G proteins (, or ) encoding genes have been identified in a significant number of tumors. Interestingly, uveal melanoma driver mutations in / were identified for a decade, but their discovery did not lead to mutation-specific drug development, unlike it the case for mutations in cutaneous melanoma which saw enormous success. Moreover, new immunotherapies strategies such as immune checkpoint inhibitors have given underwhelming results. In this review, we summarize the current knowledge on cancer-associated alterations of GPCRs and G proteins and we focus on the case of uveal melanoma. Finally, we discuss the possibilities that this signaling might represent in regard to novel drug development for cancer prevention and treatment.
肿瘤发生与G蛋白偶联受体(GPCRs)及相关G蛋白的异常表达和活性相关。在大量肿瘤中已鉴定出GPCRs和G蛋白(、或)编码基因的致癌突变。有趣的是,葡萄膜黑色素瘤驱动基因/的突变已被发现十年了,但与皮肤黑色素瘤突变取得巨大成功不同,其发现并未带来针对特定突变的药物研发。此外,诸如免疫检查点抑制剂等新的免疫治疗策略效果并不理想。在本综述中,我们总结了目前关于GPCRs和G蛋白与癌症相关改变的知识,并聚焦于葡萄膜黑色素瘤的情况。最后,我们讨论了这种信号传导在癌症预防和治疗新药研发方面可能带来的可能性。