Von Hippel-Lindau tumor suppressor pathways&corresponding therapeutics in kidney cancer

作     者：Maxwell Shulman Rachel Shi Qing Zhang Maxwell Shulman;Rachel Shi;Qing Zhang

作者机构：Department of PathologyUniversity of Texas Southwestern Medical CenterDallasTXUSA 

出 版 物：《Journal of Genetics and Genomics》 (遗传学报（英文版）)

年 卷 期：2021年第48卷第7期

页      面：552-559页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the Cancer Prevention and Research Institute of Texas(CPRIT,RR190058) the American Cancer Society(ACS)Research Scholar Award(RSG-18059-01-TBE) the National Cancer Institute(R01CA211732) the Department of Defense Kidney Cancer Research Program(KCRP)Idea Development Award(W81XWH1910813) supported by Developmental Research Program from Kidney Cancer Specialized Program of Research Excellence(SPORE)at UTSW sponsored by NCI(P50CA196516) 

主　　题：VHL HIF ccRCC Kidney cancer Hypoxia 

摘      要：The identification and application of the Von Hippel-Lindau(VHL)gene is a seminal breakthrough in kidney cancer *** and its protein p VHL are the root cause of most kidney cancers,and the cascading pathway below them is crucial for understanding hypoxia,in addition to the aforementioned tumorigenesis routes and *** reviewed the history and functions of VHL/pVHL and Hypoxia-inducible factor(HIF),their well-known activities under low-oxygen environments as an E3 ubiquitin ligase and as a transcription factor,respectively,as well as their non-canonical functions revealed ***,we discussed how their dysregulation promotes tumorigenesis:beginning with chromosome 3 p-arm(3p)loss/epigenetic methylation,followed by two-allele knockout,before the loss of complimentary tumor suppressor genes leads cells down predictable oncological *** different pathways can ultimately determine the grade,outcome,and severity of the deadliest genitourinary *** finished by investigating current and proposed schemes to therapeutically treat clear cell renal cell carcinoma(cc RCC)by manipulating the hypoxic pathway utilizing Vascular Endothelial Growth Factor(VEGF)inhibitors,mammalian target of rapamycin complex 1(mTORC1)inhibitors,small molecule HIF inhibitors,immune checkpoint blockade therapy,and synthetic lethality.