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Butti, R and Kapse, P and Bhadauriya, G and Ahmad, S and Chaubal, R and Parab , P and Kadam, R and Mahapatra, SS and Shet, T and Dutt, A and Gupta, S and Kundu GC., GC (2023) Development and characterization of a patient‑derived orthotopic xenograft of therapy‑resistant breast cancer. Oncology Report, 49 (5). p. 99.

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Abstract

Numerous years of cell line‑based studies have enhanced the current understanding of cancer and its treatment. 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 relapsed on 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 characterized using various histological and biochemical techniques. 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).

Item Type: Article
Additional Information: 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
Subjects: Cancer Biology
Depositing User: Mr. Rameshwar Nema
Date Deposited: 18 Apr 2023 11:46
Last Modified: 18 Apr 2023 11:46
URI: http://nccs.sciencecentral.in/id/eprint/1257

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