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Multi-omics analysis of the breast cancer response to palbociclib

ABSTRACT: CDK4/6 inhibitors have emerged in combination with hormone therapy as an effective treatment for HR+/HER2- breast cancer. Despite the clinical success of these drugs, challenges such as varied patient response and acquired resistance remain a significant treatment barrier. To better understand the mechanisms by which breast cancer cells respond to CDK4/6 inhibition, we conducted a multi-omics analysis in T-47D breast cancer cells profiling Palbociclib-induced changes at the gene expression, alternative splicing, and proteomic levels. We report that cell division and proliferation-related genes are often downregulated and also subject to alternative splicing changes. Additionally, we find an upregulation of estrogen response-related genes, suggesting negative feedback between CDK4/6 and upstream hormone signaling. Intriguingly, we observe an upregulation of Cyclin D1 (consistent with previous literature) but not Cyclin D3, indicating distinct and specific roles for these cyclins in the Palbociclib response. Finally, we observe that Palbociclib broadly downregulates genes essential for cell proliferation and survival, and that co-targeting CDK7 in combination additively affects proliferation, suggesting combination strategies which might be used to achieve improved therapeutic benefit. Our findings reveal both the broad patterns and specific gene- and protein-level changes that result from Palbociclib treatment, providing a key resource in understanding the response to CDK4/6 inhibitors for researchers and clinicians to improve breast cancer treatments and expand the use of CDK4/6 inhibitors to other cancers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE297939 | GEO | 2025/07/22

REPOSITORIES: GEO

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