Recent studies have identified key molecular drivers in major cancers. Research on colorectal cancer reveals that loss of the HUWE1 ubiquitin ligase promotes stemness and drug resistance by disrupting β-catenin regulation, offering a route to counteract treatment failure. Separately, AstraZeneca and Daiichi Sankyo reported positive phase 3 results for Datroway, a successor to Enhertu, in triple-negative breast cancer, heralding potential expanded treatment indications for this aggressive tumor subtype.