Targeting receptor tyrosine kinases in ovarian cancer: Genomic dysregulation, clinical evaluation of inhibitors, and potential for combinatorial therapies

Ying Wei; Sonia Erfani; David Schweer; Rafael de Gouvea; Javeria Qadir; Junfeng Shi; Kai Cheng; Dabao Wu; Rolf Craven; Yadi Wu; Thibault Olivier; Lauren A. Baldwin; Binhua Zhou; Ying Zhou; Weidong Zhao; Burton B. Yang; Frederick R. Ueland; Xiuwei H. Yang

Molecular Therapy: Oncolytics (Mar 2023)

Targeting receptor tyrosine kinases in ovarian cancer: Genomic dysregulation, clinical evaluation of inhibitors, and potential for combinatorial therapies

Ying Wei,
Sonia Erfani,
David Schweer,
Rafael de Gouvea,
Javeria Qadir,
Junfeng Shi,
Kai Cheng,
Dabao Wu,
Rolf Craven,
Yadi Wu,
Thibault Olivier,
Lauren A. Baldwin,
Binhua Zhou,
Ying Zhou,
Weidong Zhao,
Burton B. Yang,
Frederick R. Ueland,
Xiuwei H. Yang

Affiliations

Ying Wei: Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science & Technology of China, Hefei, Anhui Province, P.R. China
Sonia Erfani: Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY, USA; Pharmacy Services, University of Kentucky Medical Center, Lexington, KY, USA
David Schweer: Markey Cancer Center and College of Medicine, University of Kentucky, Lexington, KY, USA
Rafael de Gouvea: Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY, USA; College of Literature Science and Arts, University of Michigan, Ann Arbor, MI, USA
Javeria Qadir: Sunnybrook Research Institute, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Junfeng Shi: Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY, USA; Markey Cancer Center and College of Medicine, University of Kentucky, Lexington, KY, USA; Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China
Kai Cheng: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, P.R. China
Dabao Wu: Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science & Technology of China, Hefei, Anhui Province, P.R. China
Rolf Craven: Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY, USA
Yadi Wu: Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY, USA; Markey Cancer Center and College of Medicine, University of Kentucky, Lexington, KY, USA
Thibault Olivier: Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY, USA
Lauren A. Baldwin: Markey Cancer Center and College of Medicine, University of Kentucky, Lexington, KY, USA
Binhua Zhou: Markey Cancer Center and College of Medicine, University of Kentucky, Lexington, KY, USA
Ying Zhou: Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science & Technology of China, Hefei, Anhui Province, P.R. China; Corresponding author Ying Zhou, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science & Technology of China, Anhui Province, P.R. China.
Weidong Zhao: Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science & Technology of China, Hefei, Anhui Province, P.R. China; Corresponding author Weidong Zhao, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science & Technology of China, Hefei, Anhui Province, P.R. China.
Burton B. Yang: Sunnybrook Research Institute, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Corresponding author Burton B. Yang, Sunnybrook Hospital, University of Toronto, ON, Canada.
Frederick R. Ueland: Markey Cancer Center and College of Medicine, University of Kentucky, Lexington, KY, USA; Corresponding author Fred R. Ueland, Department of Obstetrics and Gynecology, Department of Pathology, and Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
Xiuwei H. Yang: Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY, USA; Corresponding author Xiuwei H. Yang, Department of Pharmacology and Nutritional Sciences and Markey Cancer Center, University of Kentucky, Lexington, KY, USA.

Journal volume & issue: Vol. 28
pp. 293 – 306

Abstract

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Epithelial ovarian cancer (EOC) remains one of the leading causes of cancer-related deaths among women worldwide. Receptor tyrosine kinases (RTKs) have long been sought as therapeutic targets for EOC, as they are frequently hyperactivated in primary tumors and drive disease relapse, progression, and metastasis. More recently, these oncogenic drivers have been implicated in EOC response to poly(ADP-ribose) polymerase (PARP) inhibitors and epigenome-interfering agents. This evidence revives RTKs as promising targets for therapeutic intervention of EOC. This review summarizes recent studies on the role of RTKs in EOC malignancy and the use of their inhibitors for clinical treatment. Our focus is on the ERBB family, c-Met, and VEGFR, as they are linked to drug resistance and targetable using commercially available drugs. The importance of these RTKs and their inhibitors is highlighted by their impact on signal transduction and intratumoral heterogeneity in EOC and successful use as maintenance therapy in the clinic through suppression of the VEGF/VEGFR axis. Finally, the therapeutic potential of RTK inhibitors is discussed in the context of combinatorial targeting via co-inhibiting proliferative and anti-apoptotic pathways, epigenomic/transcriptional programs, and harnessing the efficacy of PARP inhibitors and programmed cell death 1/ligand 1 immune checkpoint therapies.

Published in Molecular Therapy: Oncolytics

ISSN: 2372-7705 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.cell.com/molecular-therapy-family/oncolytics/latest-content

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Abstract

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