A‘Goldmine’for digging cancer-specific targets:the genes essential for embryo development but non-essential for adult life

摘要

Cancer initiation and progression are usually triggered by protooncogene activation and/or tumor suppressor gene inactivation and promoted by further genomic and epigenetic alterations that reprogram cell gene expression,metabolism,proliferation,differentiation,and behavior.Overexpressed or mutation-activated tyrosine kinase receptors and their signaling components,such as HER2,EGFR,Src,RAS,PI3K,and AKT,steroid hormone receptors,such as estrogen receptor and androgen receptor,and other cell growth and cell cycle regulators induce carcinogenesis or promote cancer cell growth,survival,and progression.Accordingly,many therapeutic drugs have been developed and used to target these molecules for treating different cancers(Supplementary Table S1).Although these drugs have significantly improved cancer treatments,most oncogenic factors are also expressed in normal cells and required for normal physiological functions.Therefore,the drugs of anti-oncogenic factors also result in severe adverse effects on cancer patients.An ideal anti-cancer drug should specifically kill cancer cells without affecting normal cellular function,which requires identifying targets essential for cancer cells but non-essential for normal cells.Importantly,these cancer-selective targets required for cancer cell survival may or may not be the classic oncogenes that have attracted extensive attention for drug development.