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Itraconazole in the Treatment of Aberrantly Active Hedgehog and/or PI3K Recurrent Ovarian Cancer

Cynthia S E Hendrikse1,2, Noortje Voeten1, Phyllis van der Ploeg1

  • 1Department of Gynecology and Obstetrics, Catharina Cancer Institute, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands.

Cancers
|May 13, 2026
PubMed
Abstract

Insights

Itraconazole did not improve progression-free survival in recurrent ovarian cancer (OC) patients with high Hedgehog (HH) or Phosphoinositide-3-kinase (PI3K) signaling. Despite limited side effects, the treatment showed no efficacy, though CA125 levels suggested potential tumor inhibition.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Recurrent ovarian cancer (OC) presents limited treatment options and a poor prognosis.
  • Targeting tumor-promoting signaling transduction pathways (STPs), including Hedgehog (HH) and Phosphoinositide-3-kinase (PI3K), offers potential therapeutic strategies.
  • This study investigates itraconazole's efficacy in treating recurrent OC with aberrant HH and/or PI3K STP activity.

Purpose of the Study:

  • To evaluate the efficacy of itraconazole as a targeted therapy for recurrent ovarian cancer (OC) with aberrant Hedgehog (HH) and/or Phosphoinositide-3-kinase (PI3K) signaling.
  • To compare progression-free survival (PFS) on itraconazole therapy (PFS2) versus prior therapy (PFS1), with a success ratio (PFS2/PFS1) of ≥1.0.
  • To assess secondary endpoints including treatment-related side effects, overall response, and one-year survival.

Main Methods:

  • Assessed HH and PI3K STP activity in recurrent OC patients.
  • Administered itraconazole to patients with high STP activity, targeting both HH and PI3K pathways.
  • Compared progression-free survival (PFS2) on itraconazole to PFS on prior therapy (PFS1) as the primary endpoint.

Main Results:

  • Of 16 patients analyzed, 93% were eligible for itraconazole therapy; 9 initiated treatment.
  • No patient achieved a PFS2/PFS1 ratio ≥ 1.0 (mean 0.26), indicating treatment ineffectiveness.
  • Side effects were predominantly grade 1-2; one-year survival was 22%, and CA125 levels rose rapidly post-treatment.

Conclusions:

  • Itraconazole monotherapy is ineffective for recurrent ovarian cancer (OC) with aberrant HH and/or PI3K activity.
  • While CA125 levels did not correlate with treatment outcome, their rapid increase after therapy cessation suggests potential tumor inhibitory effects.
  • Further research may explore combination therapies or different patient stratification strategies for targeting these pathways in OC.
Keywords:
hedgehog pathwayitraconazoleovarian neoplasmsphosphoinositide-3-kinase pathwayprecision medicineprogression-free survivalsignal transduction pathwaystargeted therapy

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