Evidence map›Paper›PMID 40904502›Full record

ArticleFrontiers in oncology2025

Combined treatment with CDK4/6, CDK2, and CXCR1/2 inhibitors effectively halts the growth of BRAF wild-type melanoma tumors.

Jinming Yang, Weifeng Luo, Patricia Ward, Sheau-Chiann Chen, John Zebala, Dean Maeda, Chi Yan, Ann Richmond

Abstract read
In one paragraph

Article in Frontiers in oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Jinming Yang *Tennessee Valley Healthcare System (TVHS) Department of Veterans Affairs, Nashville, TN, United States.
Weifeng Luo *Tennessee Valley Healthcare System (TVHS) Department of Veterans Affairs, Nashville, TN, United States.
Patricia WardDepartment of Pharmacology, Vanderbilt University, Nashville, TN, United States.
Sheau-Chiann ChenDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United States.
John ZebalaSyntrix Biosystems, Auburn, WA, United States.
Dean MaedaSyntrix Biosystems, Auburn, WA, United States.
Chi YanTennessee Valley Healthcare System (TVHS) Department of Veterans Affairs, Nashville, TN, United States.
Ann RichmondTennessee Valley Healthcare System (TVHS) Department of Veterans Affairs, Nashville, TN, United States.

Funding

Targeting the NF-kappaB Pathway in MelanomaR01CA116021 · NCI · VANDERBILT UNIVERSITY · PI RICHMOND, ANN, YAN, CHI · 2005 to 2024
$6.7M
BLRD VA I01 BX002301BLRD VA IK6 BX005225NCI NIH HHS R01 CA116021
6 · The paper itself

Abstract

Introduction: Inhibitors of cyclin-dependent kinase 4 and 6 (CDK4/6) are approved for the treatment of locally advanced or metastatic breast cancer, but not for melanoma. Methods: In this study, we evaluated the effectiveness of the CDK4/6 inhibitor, palbociclib, the CDK2 inhibitor, PF-07104091, the dual CXCR1 and CXCR2 (CXCR1/2) antagonist, SX-682, and the combination of these inhibitors for effective treatment of melanoma in preclinical models. Results: Both palbociclib and SX-682 inhibited the growth of BRAF Conclusions: The combination of all three inhibitors resulted in a tumor microenvironment characterized by increased IFNγ-producing CD4+ T cells, decreased CD4+FOXP3+ T regulatory cells (Tregs), and decreased IL-10-producing CD4+ T cells. This combination also decreased the percentage of CD8+ T cells that expressed PD-1 or TIM-3 and increased the ratio of MHCII+F4/80+ M1-like macrophages to CD206+F4/80+ M2-like macrophages. These data suggest that inhibiting CDK4/6 and CDK2, combined with antagonism of CXCR1/2, may be an effective treatment for BRAF wild-type melanoma tumors and NRAS mutant melanoma tumors that express Rb and are resistant to immune checkpoint inhibitors.

Indexed as

CDK inhibitorsCXCR2 antagonistmelanomatumor growthtumor immune microenvironment

Identifiers

PMID40904502
PMCPMC12402945

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.