# CDK4/6 Inhibitors in Breast Cancer—Who Should Receive Them?

## TL;DR

This paper explores how CDK4/6 inhibitors can be better targeted in breast cancer treatment, especially for patients with specific genetic changes.

## Contribution

The study identifies that loss of the NF1 tumor suppressor increases sensitivity to CDK4/6 inhibitors in breast cancer.

## Key findings

- NF1 loss makes tumors more reliant on CDK4/6 activity for survival.
- CDK4/6 inhibition is more effective in tumors with NF1 loss when combined with endocrine therapy.

## Abstract

More than 70% of breast cancers are estrogen receptor-positive (ER+). Endocrine therapy that blocks estrogen signaling remains the cornerstone of treatment, yet relapses continue to affect many patients. Cyclin-dependent kinases 4 and 6 (CDK4/6) regulate the G1-S phase transition in the cell cycle, and pharmacological inhibition of this pathway has been successfully leveraged to reduce recurrence. CDK4/6 inhibitors combined with endocrine therapy are now the standard of care, although determining the optimal patient population for treatment remains a key challenge. A newly published study provides important insight, showing that loss of the NF1/neurofibromin tumor suppressor confers greater sensitivity to CDK4/6 inhibition, as these tumors rely heavily on CDK4/6 activity for survival under endocrine therapy.