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The RAS-MEK-ERK pathway in low-grade serous ovarian cancer.

Elizabeth H Stover1, Elizabeth K Lee1, Geoffrey I Shapiro1

  • 1Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, United States of America; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, United States of America.

Gynecologic Oncology
|July 18, 2025
PubMed
Summary

Low-grade serous ovarian cancer (LGSC) is driven by RAS-MEK-ERK pathway mutations. Targeting this pathway with MEK inhibitors and novel KRAS inhibitors shows promise for improved LGSC treatment outcomes.

Keywords:
Low grade serous ovarian cancerRAS pathwayTargeted therapy

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Low-grade serous ovarian cancer (LGSC) is an uncommon epithelial ovarian cancer subtype.
  • LGSC often occurs in younger patients and shows limited sensitivity to platinum-based chemotherapy.
  • Genomic studies reveal frequent RAS-MEK-ERK pathway mutations in LGSC and serous borderline tumors (SBT).

Purpose of the Study:

  • To review the role of the RAS-MEK-ERK pathway in LGSC.
  • To summarize current and emerging targeted therapeutic strategies for LGSC.
  • To highlight the potential of novel inhibitors for LGSC treatment.

Main Methods:

  • Review of genomic studies identifying RAS-MEK-ERK pathway mutations (KRAS, NRAS, BRAF) in LGSC.
  • Analysis of clinical trial data for MEK inhibitors (e.g., trametinib, binimetinib) in LGSC.
  • Examination of ongoing research into novel targeted therapies, including RAF/MEK clamps and KRAS inhibitors.

Main Results:

  • MEK inhibitors like trametinib have shown clinical benefit in recurrent LGSC.
  • Some MEK inhibitors demonstrate higher response rates in tumors with KRAS mutations, though efficacy can be variable.
  • Emerging therapies like avutometinib/defactinib and novel KRAS inhibitors are under investigation.

Conclusions:

  • The RAS-MEK-ERK pathway is a critical therapeutic target in LGSC.
  • Targeted therapies, including MEK inhibitors and novel KRAS inhibitors, offer promising new treatment avenues for LGSC.
  • Continued clinical and translational research is essential to optimize RAS-MEK-ERK pathway inhibition strategies for LGSC.