How CDK4/6 Inhibitors Cause Cancer Cells to Stop Growing and What This Means for Treatment

CDK4/6 inhibitors are associated with durable tumor control and a more favorable toxicity profile in HR-positive, HER2-negative breast cancer.

• These inhibitors prevent the phosphorylation of retinoblastoma (RB) and induce cell cycle arrest during the G1 to S phase.
• Prolonged treatment with CDK4/6 inhibitors leads to cellular senescence, characterized by stable, non-dividing cells with significant changes in gene expression and secretion.
• The effects of CDK4/6 inhibitor-induced senescence vary between cancerous and normal cells, influencing the surrounding tissue environment.
• A unique secretory profile, known as the senescence-associated secretory phenotype (SASP), alters immune responses and maintains tissue balance.
• CDK4/6 inhibitors may impact the tumor microenvironment by affecting immune surveillance and interactions with surrounding tissue.
• Resistance mechanisms to CDK4/6 inhibitors and potential combination strategies are being explored, focusing on signaling pathways and immune therapies.

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