Breast cancer is one of the most prevalent cancers. Triple-negative breast cancer (TNBC) is the most aggressive and deadly of the subtypes. Most therapies are inefficient as molecular targets are poorly identified due to the molecular heterogeneity nature of TNBC. One main limitation for finding new therapeutics is the difficulty in developing genetic models for TNBC. A study in Disease Models & Mechanisms shows a Drosophila p53-Myc platform for exploring TNBC genomic complexity. Individual fly lines were generated after establishing that the mutation of TP53 and the amplification of MYC are the most common driver genes in TNBC. Myc promoted tissue overgrowth and knockdown of p53 enhanced Myc lethality without affecting the tissue or cells. Functional assays in 3-hit TNBC lines where candidate genes were overexpressed showed 49 genes to be involved as cancer drivers. This Drosophila model and the functional database obtained can help understand drug response in the future and help prognosis and drug selection for future therapeutics.

Original reference: Diaz, J.E.L. et al. Dis. Model Mech. 17, 7 (2024)

乳腺癌是最常见的癌症之一。三阴性乳腺癌 (TNBC) 是最具侵袭性和致命性的亚型。由于 TNBC 的分子异质性，分子靶点很难识别，因此大多数疗法效率低下。寻找新疗法的一个主要限制是开发 TNBC 遗传模型的困难。 《疾病模型与机制》中的一项研究展示了果蝇p53-Myc 平台，用于探索 TNBC 基因组复杂性。在确定 TP53 突变和 MYC 扩增是 TNBC 中最常见的驱动基因后，产生了个体果蝇系。 Myc促进组织过度生长， p53的敲低增强了Myc 的致死率，而不影响组织或细胞。对候选基因过表达的 3 次命中 TNBC 细胞系进行的功能分析显示，有 49 个基因与癌症驱动因素有关。这种果蝇模型和获得的功能数据库可以帮助了解未来的药物反应，并有助于未来治疗的预后和药物选择。

原始参考文献： Diaz, JEL et al.迪斯。机甲模型。 17 , 7 (2024)