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April 19, 2026Cancer Research

Abstract LB340: Mechanism-based trial matching reveals a 54% target alignment gap in ovarian cancer: Quantifying the precision-eligible ovarian cancer patients

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FKFahad Kiani

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Overview

Phase 2 trial analysis quantifies mechanism alignment gaps in ovarian cancer patients, suggesting urgent actions for better drug targeting.

Key Points

  • This study aims to quantify the gap in mechanism alignment between patients with ovarian cancer and the available trial drugs.
  • Curated trial drugs with mechanism of action annotations.
  • Computed patient tumor profiles using somatic mutations and pathway aggregation.
  • Calculated mechanism fit using similarity measures to prevent false positives.
  • Validated mechanism discrimination using a high-DDR reference profile.
  • Assessed matchability prevalence in a real ovarian cancer cohort from TCGA-OV.
  • DDR-targeting trials showed a mean fit of 0.874, compared to 0.038 for non-DDR trials, indicating strong discrimination.
  • 314 out of 585 ovarian cancer patients (53.7%) lacked strong mechanism alignment despite passing eligibility criteria.
  • Only 271 patients (46.3%) had targetable vulnerabilities aligned with current trials.
  • No significant survival difference was observed between groups, validating the prevalence of mechanism mismatch.

Cite This Study

Fahad Kiani (2026) studied this question.

synapsesocial.com/papers/69e473ff010ef96374d8fb62https://doi.org/10.1158/1538-7445.am2026-lb340
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