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Evaluating the Therapeutic Potential of MRT68921 and Afatinib in Three-Dimensional Models of Epithelial Ovarian Cancer.


ABSTRACT:

Background/objectives

Epithelial ovarian cancer (EOC) is often diagnosed at advanced stages, with metastasis driven by spheroid dissemination within the peritoneal cavity. We previously demonstrated that autophagy supports spheroid cell survival and suggest that it contributes to chemoresistance. Unc-51-like autophagy activating kinase 1 (ULK1), a key regulator of autophagy, has emerged as a promising therapeutic target. Here, we evaluated the effects of ULK1 inhibition via MRT68921, alone and in combination with afatinib-a tyrosine kinase inhibitor (TKI) known to induce pro-survival autophagy-in EOC.

Methods

High-grade serous (HGSOC) and ovarian clear cell carcinoma (OCCC) cell lines were cultured under adherent and spheroid conditions. Immunoblotting confirmed on-target ef

SUBMITTER: Johnston TPA 

PROVIDER: S-EPMC12839298 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature