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

CDK2 inhibitor PF-07104091 achieves disease stabilization in CDK4/6 inhibitor-resistant HR+/HER2- metastatic breast cancer regardless of RB status, with responses linked to TP53 retention.

• Why it matters: Overcoming resistance to CDK4/6 inhibitors remains a major challenge in treating HR+/HER2- metastatic breast cancer, limiting effective options for patients.
• What they did: The study analyzed tumor and liquid biopsies from patients treated with PF-07104091, along with experiments in cell lines, to assess its activity and mechanisms in resistant models, focusing on RB and TP53 status.
• The result: Findings show CDK2 inhibition reduces DNA replication, increases DNA damage, and inhibits mitosis independently of RB, with growth suppression dependent on p53, suggesting new therapeutic strategies for resistant breast cancer.