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The potential of RAS/RAF/MEK/ERK (MAPK) signaling pathway inhibitors in ovarian cancer: A systematic review and

C S E Hendrikse1, P M M Theelen2, P van der Ploeg1

  • 1Department of Obstetrics and Gynecology and Catharina Cancer Institute, Catharina Hospital, Eindhoven, the Netherlands; GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands.

Gynecologic Oncology
|February 25, 2023
PubMed
Abstract

Insights

MAPK inhibitors show clinical benefit in ovarian cancer (OC). MEK inhibitors are most promising as single agents, particularly for low-grade serous ovarian carcinoma (LGSOC). Dual inhibition may benefit specific patient groups.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The RAS/RAF/MEK/ERK (MAPK) pathway is implicated in ovarian carcinogenesis, with frequent activating mutations in low-grade serous ovarian carcinoma (LGSOC).
  • MAPK inhibitors are being explored for ovarian carcinoma (OC) treatment, necessitating an evaluation of their efficacy and safety.

Approach:

  • A meta-analysis was conducted on nine studies encompassing 319 OC patients to assess the effectiveness of single MAPK pathway inhibition.
  • Primary outcomes included clinical benefit rate (CBR), while secondary outcomes focused on overall response rate (ORR) and severe adverse events (Grade 3/4).

Key Points:

  • The pooled CBR for MAPK inhibitors in OC was 63%.
  • MEK inhibitors demonstrated the best efficacy as single agents, especially in LGSOC patients (CBR 87%, ORR 27%).
  • Combined Raf and MEK inhibition showed high efficacy (CBR 100%, ORR 83%) in a small subset of BRAFv600-mutated LGSOC.

Conclusions:

  • MEK inhibitors represent promising single-agent therapies for LGSOC.
  • Dual MAPK pathway inhibition warrants consideration for patients with BRAFv600 mutations or those with limited treatment options.
  • Frequent Grade 3/4 adverse events were observed, highlighting the need for careful toxicity monitoring.
Keywords:
Clinical benefitMAPK inhibitorsMAPK pathwayOvarian cancerSignal transduction pathwayTargeted therapy

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