Anticancer drugs: How to select small molecule combinations?

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.