Tumor-specific lytic path“hyperploid progression mediated death”:Resolving side effects through targeting retinoblastoma or p53 mutant

• 作者: Frank-Un Hong Miguel Castro Klaus Linse
• 来源期刊: 世界临床肿瘤学杂志:英文版
• 学科: 医学
• 关键词: Retinoblastoma protein P53 protein Cancer CHECKPOINT TAXOL Tumorspecific lytic path
• 年，卷（期）: 2020,（11）
• 页码范围: 854-867,I0001
• 页数: 16页
• 分类号: R73

摘要

A major advance was made to reduce the side effects of cancer therapy via the elucidation of the tumor-specific lytic path“hyperploid progression-mediated death”targeting retinoblastoma(Rb)or p53-mutants defective in G1 DNA damage checkpoint.The genetic basis of human cancers was uncovered through the cloning of the tumor suppressor Rb gene.It encodes a nuclear DNA-binding protein whose self-interaction is regulated by cyclin-dependent kinases.A 3Dstructure of Rb dimer is shown,confirming its multimeric status.Rb assumes a central role in cell cycle regulation and the“Rb pathway”is universally inactivated in human cancers.Hyperploidy refers to a state in which cells contain one or more extra chromosomes.Hyperploid progression occurs due to continued cell-cycling without cytokinesis in G1 checkpoint-defective cancer cells.The evidence for the triggering of hyperploid progression-mediated death in RBmutant human retinoblastoma cells is shown.Hence,the very genetic mutation that predisposes to cancer can be exploited to induce lethality.The discovery helped to establish the principle of targeted cytotoxic cancer therapy at the mechanistic level.By triggering the lytic path,targeted therapy with tumor specificity at the genetic level can be developed.It sets the stage for systematically eliminating side effects for cytotoxic cancer therapy.