Oncogene-addicted tumors present a valuable target for therapeutic intervention and an opportunity to achieve a wide therapeutic window. Nonetheless, resistance to targeted therapies is frequently observed and it arises through multiple mechanisms, including mutations in the target gene. Chromosomal instability, a defining feature of human cancer, has been linked to targeted therapy resistance, but the mechanism underlying this association is poorly understood. In the current issue of EMBO Molecular Medicine, Salgueiro et al show that chromosomal instability can lead to the generation of alternative oncogenic drivers, thereby providing the ability for cancer cells to overcome the oncogene withdrawal bottleneck. Importantly, this study shows that, by generating de novo genomic diversity, chromosomal instability serves as an adaptive response to therapeutic insult.

中文翻译：

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克服成瘾的 CINful 方法：染色体不稳定性如何使癌症克服其致癌基因成瘾。

癌基因成瘾性肿瘤为治疗干预提供了有价值的靶点，并为实现广泛的治疗窗口提供了机会。尽管如此，经常观察到对靶向治疗的耐药性，并且它是通过多种机制产生的，包括靶基因的突变。染色体不稳定性是人类癌症的一个决定性特征，它与靶向治疗耐药性有关，但人们对这种关联背后的机制知之甚少。在最新一期的 EMBO 分子医学中，Salgueiro 等人表明，染色体不稳定性可以导致替代致癌驱动因素的产生，从而为癌细胞提供克服致癌基因撤回瓶颈的能力。重要的是，这项研究表明，通过从头产生基因组多样性，染色体不稳定性可以作为对治疗损伤的适应性反应。