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

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^WT/NRAS^WT B16-F10 and NRAS^mut 1014 melanoma tumors and in both models, SX-682 created a more anti-tumor immune microenvironment. The combination effect was additive in the B16F10 model, but not in the 1014 model. In the B16F10 model

SUBMITTER: Yang J 

PROVIDER: S-EPMC12402945 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature