Evidence map›Paper›PMID 40909606›Full record

ArticlebioRxiv : the preprint server for biology2025

Charting the Multi-level Molecular Response to Palbociclib in ER-Positive Breast Cancer.

Archishma Kavalipati, Amy Aponte, Michael E Sullivan, Sarah L Whittington, José C Martínez, Grant Goda, Maria M Aleman, Michael J Emanuele, Daniel Dominguez

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Archishma KavalipatiCurriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC, USA.ORCID 0000-0003-3663-5537
Amy AponteDepartment of Pharmacology, University of North Carolina, Chapel Hill, NC, USA.ORCID 0000-0001-5929-1576
Michael E SullivanDepartment of Pharmacology, University of North Carolina, Chapel Hill, NC, USA.
Sarah L WhittingtonLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
José C MartínezLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Grant GodaDepartment of Pharmacology, University of North Carolina, Chapel Hill, NC, USA.ORCID 0000-0002-7325-2490
Maria M AlemanDepartment of Pharmacology, University of North Carolina, Chapel Hill, NC, USA.
Michael J EmanueleDepartment of Pharmacology, University of North Carolina, Chapel Hill, NC, USA.
Daniel DominguezCurriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC, USA.

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
UNC Oncology K12K12CA120780 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WILLIAM Y. KIM · 2007 to 2026
$9.6M
UNC Integrated Translational Oncology Program (UNC-iTOP)T32CA244125 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WILLIAM Y. KIM, Jen Jen Yeh · 2019 to 2026
$3.9M
Predoctoral Training in the Pharmacological SciencesT32GM135095 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph Mauro Calabrese, Michael James Emanuele · 2020 to 2026
$3.6M
Protein Disorder as a Modifier of RNA Binding and RegulationR35GM142864 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Daniel Issac Dominguez · 2021 to 2026
$2.5M
Proteostasis signaling in cell cycle controlR35GM153250 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Michael James Emanuele · 2024 to 2026
$1.9M
Triggering Aberrant RNA Processing for RCC TherapyR01CA290597 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Daniel Issac Dominguez, WILLIAM Y. KIM · 2024 to 2026
$1.9M
Cell cycle paths as a framework for understanding drug resistance in tumor cell subpopulationsR01CA280482 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Jeanette Gowen Cook, Michael James Emanuele · 2024 to 2026
$1.8M
Regulation of the retinoblastoma (Rb) tumor suppressor by the ubiquitin-proteasome systemF31CA288070 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI APONTE, AMY · 2024 to 2025
$81k
NCI NIH HHS F31 CA288070NCI NIH HHS K12 CA120780NCI NIH HHS P30 CA016086NCI NIH HHS R01 CA280482NCI NIH HHS R01 CA290597NCI NIH HHS T32 CA244125NIGMS NIH HHS R35 GM142864NIGMS NIH HHS R35 GM153250NIGMS NIH HHS T32 GM135095
6 · The paper itself

Abstract

The addition of CDK4/6 inhibitors to endocrine therapy has significantly improved outcomes in HR+/HER2-breast cancer. However, variable patient responses and acquired resistance remain a clinical challenge. We therefore defined the comprehensive molecular response to palbociclib, the most clinically used CDK4/6 inhibitor. Global analyses of gene expression, protein abundance, splicing, and chromatin accessibility revealed broad patterns and specific changes that result from CDK4/6-inhibition in breast cancer cells. We uncovered unexpected feedback between CDK4/6 and estrogen-response signaling, which has clear clinical implications. We also revealed a widespread alternative splicing program that partially overlapped with genes whose expression is regulated, and which is expected to impact protein function. These molecular changes nominated combination therapies that interfere with the activation of CDKs or ERα. Accordingly, co-targeting CDK7, which regulates CDK2, CDK4/6 and ERα, additively impacted cell fitness. Collectively, these data reveal a complex, multi-tiered response to CDK4/6 inhibition, with implications for therapeutic efficacy.

Identifiers

PMID40909606
PMCPMC12407948

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.