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

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Heba Ahmed Mohamed

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 10, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 16, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 26, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 26, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 16, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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