# Exploration of Therapeutic Targets Using CDK4 Inhibitors for Head and Neck Mucosal Melanoma

## TL;DR

This study explores CDK4 inhibitors as potential treatments for aggressive head and neck mucosal melanoma by testing their effects on cancer cell growth and signaling.

## Contribution

The study identifies CDK4 inhibitors as promising molecular-targeted therapies for mucosal melanoma through experimental and clinical validation.

## Key findings

- Abemaciclib and palbociclib showed concentration-dependent inhibition of MM cell proliferation.
- CDK4 inhibitors reduced phosphorylated RB1 levels in melanoma cell lines.
- CDK4 immunostaining was positive in 78.3% of patient samples, suggesting relevance to treatment.

## Abstract

Mucosal melanoma (MM) is an extremely aggressive malignant tumor in the head and neck region associated with a poor prognosis. In the present study, we conducted cell proliferation assay and western blotting using cell lines derived from MM and the immunohistochemical analysis of pathological MM tissues to identify novel therapeutic targets. Herein, we report on the potential of cyclin‐dependent kinase 4 (CDK4) inhibitors as molecular targeted therapies for MM.

Retrospective cohort study and laboratory analysis.

A tertiary referral center.

MTT assay and western blotting were performed on the HMV‐II (RCB0777) and GAK (JCRB0180) cell lines, treated with the CDK4 inhibitors abemaciclib (LY2835219) and palbociclib (PD‐0332991). This retrospective cohort study included patients with head and neck MM; immunohistochemistry was performed on clinical specimens.

Abemaciclib and palbociclib showed concentration‐dependent cytostatic effects on HMV‐II and GAK cells at 72 hours in the MTT assay. In western blotting, they exhibited concentration‐dependent inhibitory effects on phosphorylated RB1 in HMV‐II and GAK cells at 24 hours. Of 23 patients, 18 (78.3%) had positive results on CDK4 immunostaining. No clinicopathologic factors were significantly associated with CDK4 status.

Abemaciclib and palbociclib may suppress MM cell proliferation. The CDK4 signaling pathway is a potential target for molecular‐targeted therapies in MM.