Development and characterization of a patient-derived orthotopic xenograft of therapy-resistant breast cancer

Sep 24, 2026

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Numerous cell line-based studies have improved cancer understanding, yet treatment of hormone receptor-positive, HER2-negative metastatic breast cancers that are refractory to therapy remains limited. The study aimed to develop and characterize patient-derived orthotopic xenografts from endocrine hormone receptor-positive, HER2-negative metastatic cases that relapsed after endocrine therapy. A progressed patient’s tumor was obtained via a biobank, implanted into mice, and serially passaged to generate further PDOX generations.

LanguageEnglish

CategoryResearch & Report

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Pages10

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Abstract

Introduction

ONCOLOGY REPORTS 49: 99, 2023 Development and characterization of a patient‑derived orthotopic xenograft of therapy‑resistant breast cancer RAMESH BUTTI 1* , PRACHI KAPSE 1* , GARIMABHADAURIYA 1* , SUHAIL AHMAD2,3 , ROHAN CHAUBAL3‑5 , PALLAVI PARAB3,6 , RASIKAKADAM4,6 , SOUMYA S. MAHAPATRA7 , TANUJASHET3,8 , AMIT DUTT2,3 , SUDEEP GUPTA3,4,6 and GOPAL C. KUNDU 1,7,9 1Laboratory of Tumor Biology, Angiogenesis and Nanomedicine Research, National Centre for Cell Science, Pune, Maharashtra 411007; 2Integrated Cancer Genomics Laboratory, Tata Memorial Centre‑Advanced Centre for Treatment, Research and Education in Cancer (TMC‑ACTREC), Navi Mumbai, Maharashtra 410210; 3Homi Bhabha National Institute, Training School Complex, Mumbai 400094; 4Clinical Genomics and Hypoxia Lab (Clinician Scientist Lab), TMC‑ACTREC, Navi Mumbai, Maharashtra 410210; Departments of 5Surgical Oncology and 6Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra 400012; 7School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT) Deemed to be University, Bhubaneswar, Odisha 751024; 8Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra 400012; 9Kalinga Institute of Medical Sciences, KIIT Deemed to be University, Bhubaneswar 751016, India Received April 4, 2022; Accepted December 5, 2022 DOI: 10. 3892/or.2023.8536 Abstract. Numerous years of cell line‑based studies have enhanced the current understanding of cancer and its treat‑ ment. However, limited success has been achieved in treating hormone receptor‑positive, HER2‑negative metastatic breast cancers that are refractory to treatment. The majority of cancer cell lines are unsuitable for use as pre‑clinical models that mimic this critical and often fatal clinical type, since they are derived from treatment‑naive or non‑metastatic breast cancer cases. The aim of the present study was to develop and characterize patient‑derived orthotopic xenografts (PDOXs) from patients with endocrine hormone receptor‑positive, HER2‑negative metastatic breast cancer who had relapsedon therapy. A patient who progressed on endocrine hormone therapy provided her tumor via a biobank. This tumor was implanted in mice . It was then serially passaged by implanting PDOX tumor fragments into another set of mice to develop further generations of PDOXs. These tissues were Correspondence to: Professor Gopal C. Kundu, School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT) Deemed to be University, Campus 11, KIIT Road, Patia, Bhubaneswar, Odisha 751024, India E‑mail: [gopalc.kundu@kiit.ac.in](gopalc.kundu@kiit.ac.in) Present address: Dr Ramesh Butti, Kidney Cancer Program, Simmons Comprehensive Cancer Centre, UT Southwestern Medical Center, Dallas, TX 75235, USA *Contributed equally Key words: breast cancer, patient‑derived orthotopic xenograft, estrogen receptor‑α , progesterone receptor‑α , HER2, biomarker characterized using various histological and biochemical tech‑ niques. Histological, immunofluorescence and western blot analyses indicated that the PDOX tumors retained a similar morphology, histology and subtype‑specific molecular features to that of the patient's tumor. The present study successfully established PDOXs of hormone‑resistant breast cancer and characterized them in comparison with those derived from the original breast cancer tissue of the patient. The data highlight the reliability and usefulness of PDOX models for studies of biomarker discovery and preclinical drug screening. The present study was registered with the clinical trial registry of India (CTRI; registration no. CTRI/2017/11/010553; registered on 17/11/2017) . Introduction Breast cancer accounts for the highest mortality among female cancer patients in India (1) . It is also the most prevalent cancer type among Indian females with an estimated age‑adjusted rate of 25.8 per 100,000 women and a mortality rate of 12.7 per 100,000 women (2). India has a worse survival outcome f

FAQs

What clinical problem does the study address?

It targets endocrine hormone receptor-positive, HER2-negative metastatic breast cancers that are refractory to treatment and have limited success with current therapies.

How were the patient-derived orthotopic xenografts (PDOXs) generated?

A relapsed patient’s tumor from a biobank was implanted in mice, and tumor fragments were serially passaged into additional mice to generate further PDOX generations.

How were the PDOX models characterized?

Histological, immunofluorescence, and western blot analyses were used to verify that PDOX tumors retained morphology, histology, and subtype-specific molecular features similar to the patient’s original tumor.

Sep 24, 2026

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