CDK2 Inhibition Exerts RB-Independent Antitumor Activity in CDK4/6 Inhibitor-Resistant HR+/HER2- Breast Cancer.

CDK2 inhibitors induce RB-independent tumor suppression in CDK4/6 inhibitor-resistant HR+/HER2- breast cancer, with disease stabilization observed in patients.

• Why it matters: Overcoming resistance to CDK4/6 inhibitors remains a major challenge in treating hormone receptor-positive, HER2-negative metastatic breast cancer, limiting therapeutic options and outcomes.
• What they did: Researchers analyzed biopsies from patients treated with the selective CDK2 inhibitor PF-07104091, alongside cell line studies, to evaluate its efficacy and mechanisms in resistant tumors, focusing on RB and TP53 status.
• The result: PF-07104091 achieved disease stabilization regardless of RB expression, with growth suppression dependent on p53, suggesting CDK2 as a promising target to overcome resistance and enhance combination therapies.