Prognostic Value of (DHODH) Expression in (HGSOC): A Comparative Study Between Neoadjuvant and Adjuvant Chemotherapy Settings (HGSOC)

January 16, 2026 updated by: Heba Ahmed Mohamed

Prognostic Value of Dihydroorotate Dehydrogenase (DHODH) Expression in High-Grade Serous Ovarian Carcinoma: A Comparative Study Between Neoadjuvant and Adjuvant Chemotherapy Settings

  • To compare DHODH protein expression in HGSC tissues from patients undergoing Primary Debulking Surgery (PDS - Chemo-naive) versus Interval Debulking Surgery (IDS - Post-NACT).
  • To evaluate the association between DHODH expression and the degree of chemotherapy response (using the Chemotherapy Response Score - CRS for NACT cases).
  • To determine the prognostic value of DHODH expression in predicting Platinum-Free Interval (PFI) ,Progression -Free Survival (PFS) and Overall Survival (OS) across both groups.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

High-grade serous ovarian carcinoma (HGSC) is the most aggressive and lethal subtype of epithelial ovarian cancer, accounting for nearly 70% of ovarian cancer-related deaths worldwide (1). Despite initial sensitivity to platinum-based chemotherapy, the majority of patients eventually develop chemoresistant disease, leading to recurrence and poor long-term survival (2). The biological mechanisms underlying platinum resistance remain incompletely understood, but increasing evidence indicates that metabolic reprogramming and redox adaptation play a central role in tumor cell survival under therapeutic stress (3).

Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation, and it has recently emerged as an important vulnerability in cancer cells exposed to chemotherapy (4). Cancer cells that survive platinum-based therapy frequently upregulate antioxidant and lipid-repair systems that protect them from ferroptotic death (5). Among these systems, dihydroorotate dehydrogenase (DHODH), a mitochondrial enzyme involved in de novo pyrimidine biosynthesis, has been identified as a key suppressor of mitochondrial lipid peroxidation and ferroptosis (6).

DHODH is localized on the inner mitochondrial membrane and catalyzes the oxidation of dihydroorotate to orotate, coupling pyrimidine synthesis to the mitochondrial respiratory chain (7). Recent work has shown that DHODH acts in parallel with glutathione peroxidase-4 (GPX4) to protect cells from ferroptosis, particularly within the mitochondrial compartment (8). Inhibition of DHODH sensitizes cancer cells to oxidative damage and restores ferroptotic cell death, especially in tumors with high mitochondrial metabolism.

In ovarian cancer, platinum resistance has been linked to enhanced mitochondrial function, redox buffering, and metabolic plasticity ( 9). Neoadjuvant chemotherapy (NACT), which is increasingly used in advanced HGSC, exposes tumor cells to intense oxidative and genotoxic stress prior to surgical removal (10). This creates a strong evolutionary pressure favoring tumor clones capable of surviving chemotherapy-induced metabolic and redox stress.

However, the expression and clinical significance of DHODH in HGSC, particularly in the context of neoadjuvant chemotherapy exposure, has not been systematically investigated. No studies have directly compared DHODH expression in chemo-naïve primary debulking surgery (PDS) specimens versus post-NACT interval debulking surgery (IDS) specimens, nor correlated DHODH with chemotherapy response and survival outcomes. Understanding whether NACT selects for DHODH-high, ferroptosis-resistant tumor cells could provide novel insights into platinum resistance and identify a new therapeutic vulnerability in HGSC.

Study Type

Observational

Enrollment (Estimated)

72

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Egypt
      • Asyut, Egypt
        • Assiut University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Archived formalin-fixed paraffin-embedded (FFPE) tissue blocks from patients diagnosed with high-grade serous ovarian carcinoma will be retrieved from the pathology archives

Description

Inclusion Criteria:

  • Histologically confirmed high-grade serous ovarian carcinoma
  • Availability of adequate FFPE tumor tissue
  • Known treatment modality (PDS or IDS)
  • Available clinical follow-up including platinum-free interval and survival data

Exclusion Criteria:

  • Non-serous histological subtypes
  • Low-grade serous carcinoma
  • Inadequate tissue for immunohistochemistry
  • Missing clinical or follow-up data

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group A chemo naive and Group B neoadjuvant group

Group A (Chemo-naïve group) 36 Patients who underwent primary debulking surgery (PDS) followed by adjuvant platinum-based chemotherapy.

Group B (Neoadjuvant group) 36 Patients who received 3-4 cycles of platinum-based neoadjuvant chemotherapy followed by interval debulking surgery (IDS).
Other: Immunohistochemical (IHC) assessment of DHODH expression
Comparative analysis of DHODH expression in adjuvant and neoadjuvant groups and correlate its expression with clinical outcomes
Other: No interventions as it is observational study
No interventions as itis observational study
Group A (Chemo-naïve group) 36 Patients and Group B (neoadjuvant) group

Group A (Chemo-naïve group) 36 Patients who underwent primary debulking surgery (PDS) followed by adjuvant platinum-based chemotherapy.

Group B (Neoadjuvant group) 36 Patients who received 3-4 cycles of platinum-based neoadjuvant chemotherapy followed by interval debulking surgery (IDS).
Other: Immunohistochemical (IHC) assessment of DHODH expression
Comparative analysis of DHODH expression in adjuvant and neoadjuvant groups and correlate its expression with clinical outcomes
Other: No interventions as it is observational study
No interventions as itis observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
DHODH expression and patient survival
Time Frame: from diagnosis up to last follow up or death ( up to 96 months).
To evaluate the prognostic impact of DHODH expression in high-grade serous ovarian carcinoma by assessing its correlation with survival outcomes (overall survival and/or progression-free survival) and comparing patients treated with neoadjuvant versus adjuvant chemotherapy.
from diagnosis up to last follow up or death ( up to 96 months).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Heba Ahmed Mohamed

Collaborators

Assiut University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

July 1, 2027

Study Registration Dates

First Submitted

January 10, 2026

First Submitted That Met QC Criteria

January 16, 2026

First Posted (Actual)

January 26, 2026

Study Record Updates

Last Update Posted (Actual)

January 26, 2026

Last Update Submitted That Met QC Criteria

January 16, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DHODH in HGSOC
  • assiut university (Other Identifier: assiut university)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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