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 S1Supplementary 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.

中文翻译：

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挖掘癌症特异性靶标的“金矿”：胚胎发育所必需的基因，但对成年生活非必需。

癌症的发生和进展通常由原癌基因激活和/或肿瘤抑制基因失活触发，并由重新编程细胞基因表达、代谢、增殖、分化和行为的进一步基因组和表观遗传改变促进。过度表达或突变激活的酪氨酸激酶受体及其信号成分，如 HER2、EGFR、Src、RAS、PI3K 和 AKT，类固醇激素受体，如雌激素受体和雄激素受体，以及其他细胞生长和细胞周期调节剂诱导致癌作用或促进癌细胞生长、存活和进展。因此，已经开发出许多治疗药物并用于靶向这些分子以治疗不同的癌症（补充表 S1 补充表 S1）。尽管这些药物显着改善了癌症治疗，大多数致癌因子也在正常细胞中表达，是正常生理功能所必需的。因此，抗癌因子药物对癌症患者也造成了严重的不良反应。理想的抗癌药物应该在不影响正常细胞功能的情况下特异性杀死癌细胞，这需要确定对癌细胞必不可少但对正常细胞非必需的靶标。重要的是，癌细胞存活所需的这些癌症选择性靶标可能是也可能不是已经引起药物开发广泛关注的经典癌基因。理想的抗癌药物应该在不影响正常细胞功能的情况下特异性杀死癌细胞，这需要确定对癌细胞必不可少但对正常细胞非必需的靶标。重要的是，癌细胞存活所需的这些癌症选择性靶标可能是也可能不是已经引起药物开发广泛关注的经典癌基因。理想的抗癌药物应该在不影响正常细胞功能的情况下特异性杀死癌细胞，这需要确定对癌细胞必不可少但对正常细胞非必需的靶标。重要的是，癌细胞存活所需的这些癌症选择性靶标可能是也可能不是已经引起药物开发广泛关注的经典癌基因。