Data from Short- and Long-Term Effects of CDK4/6 Inhibition on Early-Stage Breast Cancer

• DOI: 10.1158/1535-7163.c.6538270.v1
• Publication Date: 2024-03-12T16:49:06Z
• Authors: William B. Kietzman; Garrett T. Graham; Virginie Ory; Ghada M. Sharif; Max H. Kushner; Gregory T. Gallanis; Bhaskar Kallakury; Anton Wellstein; Anna T. Riegel

<div>Abstract<p>CDK4/6 inhibitors are used in the treatment of advanced estrogen receptor (ER)(+) breast cancer. Their efficacy ER(−) and early-stage cancer is currently under investigation. Here, we show that palbociclib, a CDK4/6 inhibitor, can inhibit both progression ductal carcinoma <i>in situ</i> (DCIS) growth invasive disease an basal model (MCFDCIS) ER(+) luminal (MCF7 intraductal injection). In MCFDCIS cells, palbociclib repressed cell-cycle gene expression, inhibited proliferation, induced senescence, normalized tumorspheres formed Matrigel while formation acini by normal mammary epithelial cells (MCF10A) was not affected. Palbociclib mice with tumors their malignant reduced proliferation lesions. Transcriptomic analysis tumor stromal cell compartments showed cycle senescence genes, <i>MUC16</i>, ovarian biomarker gene, were during treatment. Knockdown <i>MUC16</i> lesions but DCIS. After cessation genes associated differentiation, for example, <i>P63</i>, inflammation, IFNγ response, antigen processing presentation remained suppressed surrounding stroma. We conclude prevent DCIS antiproliferative mediated part via MUC16. Lasting effects inhibition after drug withdrawal on differentiation immune response could impact approach to cancer.</p></div>