Synergistic effects of the combination of trametinib and alpelisib in anaplastic thyroid cancer with BRAF and PI3KCA co-mutations.

ABSTRACT:

Background

Anaplastic thyroid cancer (ATC), a rare and aggressive malignancy with a poor prognosis, has shown promise with the approved dabrafenib/trametinib combination for BRAF^V600E mutation. Co-occurring PI3KCA mutations, identified as negative prognostic factors in lung cancer with BRAF^V600E mutation, emphasize the need to target both pathways. Exploring trametinib and alpelisib combination becomes crucial for ATC.

Methods

A patient-derived xenograft (PDX) and primary cell line were obtained from an ATC patient with BRAF and PI3KCA co-mutation. Individual testing of targeted therapies against BRAF, MEK, and PI3KCA was followed by a combination treatment. Synergistic effects were evaluated using the combination index. Immunoblotting assessed the effi

SUBMITTER: Chen CP 

PROVIDER: S-EPMC10990975 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature