Mishra Sanjay, Charan Manish, Verma Ajeet Kumar, Ramaswamy Bhuvaneswari, Ahirwar Dinesh Kumar, Ganju Ramesh K
Department of Pathology, Wexner Medical Center, College of Medicine, The Ohio State University, Columbus, OH, United States.
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States.
Front Cell Dev Biol. 2021 Apr 30;9:601929. doi: 10.3389/fcell.2021.601929. eCollection 2021.
Recent studies revealed that ethnic differences in mechanistic target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK-1/2) signaling pathways might be associated with the development and progression of different human malignancies. The African American (AA) population has an increased rate of cancer incidence and mortality compared to the Caucasian American (CA) population. Although the socioeconomic differences across different ethnic groups contribute to the disparity in developing different cancers, recent scientific evidence indicates the association of molecular and genetic variations in racial disparities of different human malignancies. The mTOR and ERK-1/2 signaling pathways are one of the well-known oncogenic signaling mechanisms that regulate diverse molecular and phenotypic aspects of normal as well as cancer cells in response to different external or internal stimuli. To date, very few studies have been carried out to explore the significance of racial disparity with abnormal mTOR and ERK-1/2 kinase signaling pathways, which may contribute to the development of aggressive human cancers. In this review, we discuss the differential regulation of mTOR and ERK-1/2 kinase signaling pathways across different ethnic groups, especially between AA and CA populations. Notably, we observed that key signaling proteins associated with mTOR and ERK-1/2 pathway including transforming growth factor-beta (TGF-β), Akt, and VEGFR showed racially disparate expression in cancer patients. Overall, this review article encompasses the significance of racially disparate signaling molecules related to mTOR/ERK1/2 and their potential in developing tailor-made anti-cancer therapies.
近期研究表明,雷帕霉素作用靶点(mTOR)和细胞外信号调节激酶(ERK-1/2)信号通路的种族差异可能与不同人类恶性肿瘤的发生和发展有关。与美国白种人(CA)相比,非裔美国人(AA)的癌症发病率和死亡率更高。尽管不同种族间的社会经济差异导致了不同癌症发病的差异,但最近的科学证据表明,不同人类恶性肿瘤种族差异中的分子和基因变异存在关联。mTOR和ERK-1/2信号通路是众所周知的致癌信号机制之一,可响应不同的外部或内部刺激,调节正常细胞和癌细胞的多种分子和表型特征。迄今为止,很少有研究探讨mTOR和ERK-1/2激酶信号通路异常与种族差异的意义,而这可能导致侵袭性人类癌症的发生。在本综述中,我们讨论了不同种族间,尤其是AA和CA人群中mTOR和ERK-1/2激酶信号通路的差异调节。值得注意的是,我们观察到与mTOR和ERK-1/2通路相关的关键信号蛋白,包括转化生长因子-β(TGF-β)、Akt和VEGFR,在癌症患者中表现出种族差异表达。总体而言,这篇综述文章涵盖了与mTOR/ERK1/2相关的种族差异信号分子的意义及其在开发定制抗癌疗法中的潜力。