Precision cancer medicine is a tailored treatment approach for individual cancer patients with different genomic characteristics. Mutated or hyperactive oncogenes have served as main drug targets in current precision cancer medicine, while defective or inactivated tumor suppressors in general have not been considered as druggable targets. Synthetic lethality is one of very few approaches that enable to target defective tumor suppressors with pharmacological agents. Synthetic lethality exploits cancer cell dependency on a protein or pathway, which arises when the function of a tumor suppressor is defective. This approach has been proven to be effective in clinical settings since the successful clinical introduction of BRCA-PARP synthetic lethality for the treatment of breast and ovarian cancer with defective BRCA. Subsequently, large-scale screenings with RNAi, CRISPR/Cas9-sgRNAs, and chemical libraries have been applied to identify synthetic lethal partners of tumor suppressors. Natural products are an important source for the discovery of pharmacologically active small molecules. However, little effort has been made in the discovery of synthetic lethal small molecules from natural products. This review introduces recent advances in the discovery of natural products targeting cancer cell dependency and discusses potentials of natural products in the precision cancer medicine.

精准癌症医学是针对具有不同基因组特征的个体癌症患者量身定制的治疗方法。突变或过度活跃的癌基因已成为当前精准癌症医学的主要药物靶点，而有缺陷或失活的肿瘤抑制基因一般不被视为可药物靶点。合成致死率是为数不多的能够用药物靶向有缺陷的肿瘤抑制因子的方法之一。合成致死性利用癌细胞对蛋白质或通路的依赖性，这种依赖性在肿瘤抑制因子的功能有缺陷时出现。自从 BRCA-PARP 合成致死性成功临床引入用于治疗具有缺陷 BRCA 的乳腺癌和卵巢癌以来，这种方法已被证明在临床环境中是有效的。随后，RNAi、CRISPR/Cas9-sgRNA 和化学文库的大规模筛选已被用于鉴定肿瘤抑制因子的合成致死伙伴。天然产物是发现具有药理活性的小分子的重要来源。然而，在从天然产物中发现合成致死小分子方面几乎没有做出任何努力。本综述介绍了针对癌细胞依赖性的天然产物发现的最新进展，并讨论了天然产物在精准癌症医学中的潜力。在从天然产物中发现合成的致命小分子方面几乎没有做出任何努力。本综述介绍了针对癌细胞依赖性的天然产物发现的最新进展，并讨论了天然产物在精准癌症医学中的潜力。在从天然产物中发现合成的致命小分子方面几乎没有做出任何努力。本综述介绍了针对癌细胞依赖性的天然产物发现的最新进展，并讨论了天然产物在精准癌症医学中的潜力。