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

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)293-306
Number of pages14
JournalMolecular Therapy Oncolytics
Volume28
DOIs
StatePublished - Mar 16 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Keywords

  • EGFR
  • ERBB2
  • MET
  • VEGFR
  • ovarian cancer
  • receptor tyrosine kinases
  • targeted therapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Pharmacology (medical)

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