학술논문
AKT Isoforms Interplay in High-Grade Serous Ovarian Cancer Prognosis and Characterization.
Document Type
Academic Journal
Author
Azzalini E; Department of Medical Sciences (DSM), University of Trieste, 34147 Trieste, Italy.; Pathology Unit, IRCCS CRO Aviano-National Cancer Institute, 33081 Aviano, Italy.; Tierno D; Department of Medical Sciences (DSM), University of Trieste, 34147 Trieste, Italy.; Bartoletti M; Unit of Medical Oncology and Cancer Prevention, Department of Medical Oncology, IRCCS CRO Aviano-National Cancer Institute, 33081 Aviano, Italy.; Department of Medicine (DAME), University of Udine, 33100 Udine, Italy.; Barbazza R; Department of Medical Sciences (DSM), University of Trieste, 34147 Trieste, Italy.; Giorda G; Unit of Gynecologic Oncology Surgery, IRCCS CRO Aviano, National Cancer Institute, 33081 Aviano, Italy.; Puglisi F; Unit of Medical Oncology and Cancer Prevention, Department of Medical Oncology, IRCCS CRO Aviano-National Cancer Institute, 33081 Aviano, Italy.; Department of Medicine (DAME), University of Udine, 33100 Udine, Italy.; Cecere SC; Istituto Nazionale Tumori IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy.; Losito NS; Istituto Nazionale Tumori IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy.; Russo D; Istituto Nazionale Tumori IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy.; Stanta G; Department of Medical Sciences (DSM), University of Trieste, 34147 Trieste, Italy.; Canzonieri V; Department of Medical Sciences (DSM), University of Trieste, 34147 Trieste, Italy.; Pathology Unit, IRCCS CRO Aviano-National Cancer Institute, 33081 Aviano, Italy.; Bonin S; Department of Medical Sciences (DSM), University of Trieste, 34147 Trieste, Italy.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101526829 Publication Model: Electronic Cited Medium: Print ISSN: 2072-6694 (Print) Linking ISSN: 20726694 NLM ISO Abbreviation: Cancers (Basel) Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2072-6694
Abstract
High-grade serous ovarian cancer (HGSOC) is among the deadliest gynecological malignancies. The acquired resistance to platinum-based therapies and the intrinsic heterogeneity of the disease contribute to the low survival rate. To improve patients' outcomes, new combinatorial approaches able to target different tumor vulnerabilities and enhance the efficacy of the current therapies are required. AKT inhibitors are promising antineoplastic agents able to act in synergy with PARP inhibitors, but the spectrum of patients who can benefit from this combination is unclear, since the role of the three different isoforms of AKT is still unknown. Here, we study the expression of AKT isoforms on a retrospective cohort of archive tissue by RT-droplet digital PCR (ddPCR) analyzing their association with the clinicopathological features of patients. Based on AKT1/AKT2 and AKT1/AKT3 ratios, we define four AKT classes which were related to patients' survival, tumor morphology and BRCA1 expression. Moreover, our results show that high AKT3 expression levels were frequently associated with tumors having classic features, a low number of mitoses and the presence of psammoma bodies. Overall, our study obtains new insights on AKT isoforms and their associations with the clinicopathological features of HGSOC patients. These evidences could help to better define the subsets of patients who can benefit from AKT and PARP inhibitors therapy in future clinical trials.