Targeting the PI3K/AKT/mTOR pathway in epithelial ovarian cancer, therapeutic treatment options for platinum-resistant ovarian cancer

Journal article

Gene fusions are common in high-grade serous ovarian cancer (HGSC). Such genetic lesions may promote tumorigenesis, but the pathogenic mechanisms are currently poorly understood. Here, we investigated the role of a PIK3R1-CCDC178 fusion identified from a patient with advanced HGSC. We show that the fusion induces HGSC cell migration by regulating ERK1/2 and increases resistance to platinum treatment. Platinum resistance was associated with rod and ring-like cellular structure formation. These structures contained, in addition to the fusion protein, CIN85, a key regulator of PI3K-AKT-mTOR signaling. Our data suggest that the fusion-driven structure formation induces a previously unrecognized cell survival and resistance mechanism, which depends on ERK1/2-activation

Authors: Rinne, N; Christie, EL; Ardasheva, A; Kwok, CH; Demchenko, N

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: OAE Publishing
• Journal: Cancer Drug Resistance
• Volume: 4
• Issue: 3
• Pages: 573-595
• Publication date: 2021-01-01
• DOI: 10.20517/cdr.2021.05
• EISSN: 2578-532X
• ISSN: 2578-532X
• Language: English
• Keywords: Oncology; Cancer; PI3K/AKT/mTOR pathway; Cell biology; Ovarian cancer; Cancer research; Protein kinase B; Signal transduction; P110α; PTEN; Internal medicine; Medicine; Biology