Patient-Derived Organoids to Functionally Characterize Chemotherapy Resistance in Breast Cancer

NCT07516626 | Not Yet Recruiting

• 1 other identifier: ATLAS-BC-PDO-2026-01
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective observational study aims to functionally characterize chemotherapy resistance in patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy. Despite standard molecular classification, significant heterogeneity in treatment response exists, and the biological mechanisms underlying chemoresistance remain incompletely understood. In this study, patient-derived organoid (PDO) models will be established from tumor tissues obtained during routine clinical care. These three-dimensional models preserve the biological characteristics of individual tumors and enable ex vivo functional assessment of drug response. Chemotherapy sensitivity and resistance will be evaluated using quantitative parameters including Half-Maximal Inhibitory Concentration (IC50) values, cell viability, and apoptotic response. Functional data obtained from PDO models will be correlated with clinical and pathological treatment outcomes, particularly pathological complete response (pCR), to assess the predictive value of PDO-based assays. In addition, apoptotic biomarkers such as Caspase-3/7 will be measured in serum samples collected during routine clinical evaluation and analyzed in relation to treatment response. Furthermore, selected Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved small molecules will be tested in PDO models to evaluate their potential to reverse chemotherapy resistance, supporting drug repurposing strategies. This study aims to establish a functional, patient-specific platform for assessing chemoresistance and to contribute to the development of personalized therapeutic approaches in breast cancer.

Conditions

Breast Cancer; Locally Advanced Breast Cancer (LABC)

Keywords

Neoadjuvant Chemotherapy; Chemotherapy Resistance; Patient-Derived Organoids; Drug Repurposing; Pathological Complete Response; Ex Vivo Drug Testing; Locally Advanced Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Correlation Between PDO-Based Chemotherapy Response Metrics and Pathological Complete Response (pCR)

  Assessment of the association between functional drug response parameters obtained from patient-derived organoid (PDO) models (including Half-Maximal Inhibitory Concentration (IC50) values, cell viability, and apoptotic response) and pathological complete response (pCR) following neoadjuvant chemotherapy.

  At completion of neoadjuvant chemotherapy (approximately 6 months)

Secondary Outcomes (4)

• Association Between PDO-Derived Drug Sensitivity Metrics and Clinical Chemotherapy Resistance

  At baseline (prior to initiation of neoadjuvant chemotherapy) and at completion of treatment (approximately 6 months)

• Serum Apoptotic Biomarkers and Their Association With Treatment Response

  At baseline, during neoadjuvant chemotherapy, and at completion of treatment (approximately 6 months)

• Evaluation of Drug Repurposing Strategies in PDO Models

  Within 6 months after sample collection

• Development of Functional Predictive Models for Chemotherapy Response

  Within 12 months after completion of data collection

Study Arms (1)

Locally Advanced Breast Cancer Patients Cohort

Adult female patients diagnosed with locally advanced breast cancer and scheduled to receive standard neoadjuvant chemotherapy. Tumor tissue and blood samples obtained during routine clinical care will be used to generate patient-derived organoid models and to perform biomarker analyses. No experimental intervention will be applied to participants.

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult female patients diagnosed with locally advanced breast cancer and scheduled to receive neoadjuvant chemotherapy at a tertiary academic center. All participants will be recruited prospectively and followed during the course of standard clinical treatment.

You may qualify if:

• Female patients aged 18 years or older
• Histologically confirmed locally advanced breast cancer
• Planned to receive neoadjuvant chemotherapy
• Availability of tumor tissue obtained during routine diagnostic or therapeutic procedures
• Availability of clinical and pathological treatment data
• Ability to provide written informed consent

You may not qualify if:

• Age under 18 years
• Metastatic breast cancer
• Prior systemic chemotherapy or targeted therapy for the current diagnosis
• Presence of another active malignancy
• Severe comorbid conditions that may interfere with study participation
• Insufficient biological sample for organoid generation or analysis
• Inability or unwillingness to provide informed consent

Sponsors & Collaborators

• Atlas University: lead

Study Sites (1)

Istanbul Atlas University Faculty of Medicine

Istanbul, Turkey (Türkiye)

Location

Biospecimen

Retention: SAMPLES WITH DNA

Tumor tissue samples obtained during routine diagnostic or therapeutic procedures will be used to establish patient-derived organoid (PDO) cultures. These samples preserve tumor architecture and allow functional drug response analyses. In addition, serum samples collected during routine clinical evaluation will be retained for biomarker analysis, including apoptotic markers such as Caspase-3/7. All biospecimens will be processed, stored, and maintained under standardized laboratory conditions, and may be used for downstream molecular analyses, including Deoxyribonucleic acid (DNA) and Ribonucleic acid (RNA) based studies.

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Emine Yildirim

  Istanbul Atlas University Faculty of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emine Yildirim, MD

CONTACT

+905056234825; emine.yildirim@atlas.edu.tr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of General Surgery, Head of the Department of General Surgery

Study Record Dates

• First Submitted: April 1, 2026
• First Posted: April 8, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-03

Locations

TU (1)