Small molecules are at the forefront of anticancer therapies. Successive treatments with single molecules incur drug resistance, calling for combination. Here, we explore the tough choices oncologists face – not just which drugs to use but also the best treatment plans, based on factors such as target proteins, pathways, and gene expression. We consider the reality of cancer’s disruption of normal cellular processes, highlighting why it’s crucial to understand the ins and outs of current treatment methods. The discussion on using combination drug therapies to target multiple pathways sheds light on a promising approach while also acknowledging the hurdles that come with it, such as dealing with pathway crosstalk. We review options and provide examples and the mechanistic basis, altogether providing the first comprehensive guide to combinatorial therapy selection.

中文翻译：

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抗癌药物：小分子组合如何选择？


小分子处于抗癌疗法的前沿。连续使用单分子治疗会产生耐药性，需要联合治疗。在这里，我们探索肿瘤学家面临的艰难选择——不仅是使用哪些药物，而且是基于靶蛋白、通路和基因表达等因素的最佳治疗计划。我们考虑癌症破坏正常细胞过程的现实，强调为什么了解当前治疗方法的细节至关重要。关于使用联合药物疗法靶向多种途径的讨论揭示了一种有前途的方法，同时也承认随之而来的障碍，例如处理途径串扰。我们回顾了各种选择并提供了示例和机制基础，共同为组合疗法选择提供了第一个全面的指南。