Science Spotlight: CDK4/6 resistance that a mutation panel can’t see

A cluster of recent papers suggests that resistance to CDK4/6 inhibitors in ER+/HER2– breast cancer involves how tumor cells regulate genes and rewire metabolism, not only new mutations.

CDK4/6 inhibitors plus endocrine therapy anchor first-line treatment for advanced disease. After progression, actionable alterations such as mutations in ESR1, the gene encoding ER, increasingly guide the next treatment choice. These mutations can keep the receptor active despite estrogen deprivation, providing a rationale for drugs that degrade the receptor...