High-throughput drug screening in advanced pre-clinical 3D melanoma models identifies potential first-line therapies for NRAS-mutated melanoma.

ABSTRACT:

Background

Despite significant advances in targeted (BRAFi + MEKi) and immune (anti-PD1/PD-L1, anti-CTLA4, and anti-LAG3) therapies, treatment options for NRAS^mut melanoma remain limited. Currently, NRAS^mut patients rely on immune checkpoint inhibitors, classical chemotherapy, and off-label MEK inhibitors, with over 50% experiencing rapid disease progression. One of the key challenges in developing effective targeted therapies is the lack of preclinical models that accurately recapitulate the tumor microenvironment (TME) and the intrinsic resistance of melanoma cells bearing NRAS mutations.

Methods

To address this, we performed high-throughput screening (HTS) of over 1,300 compounds in 3D NRAS^mut melanoma spheroids. A multi-step analysis was

SUBMITTER: Angeli C 

PROVIDER: S-EPMC12487241 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature