PROTAC-mediated degradation of Bcl-xL potentiates target therapy in preclinical melanoma models.

ABSTRACT:

Background

Bcl-xL plays an important role in tumors from different origins, including melanoma, and for this reason it has been widely targeted with small-molecule BH3 mimetics, which unfortunately show several adverse effects. To overcome this limitation, selective Bcl-xL proteolysis-targeting chimera degraders have been developed. Among these, DT2216, a candidate in phase I/II clinical trials, has demonstrated antitumoral activity in preclinical cancer models from different origins, not including melanoma.

Methods

By using several established and patient-derived BRAF wild type and mutated melanoma cells, we performed western blot analysis and MTT assay to study DT2216 effect on Bcl-xL protein levels and cell viability, respectively. Combination studies were performed on BR

SUBMITTER: Valentini E 

PROVIDER: S-EPMC12870073 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature