Establishment of chemosensitivity tests in triple-negative and BRCA-mutated breast cancer patient-derived xenograft models


Autoři: Hyung Seok Park aff001;  Jeong Dong Lee aff002;  Jee Ye Kim aff001;  Seho Park aff001;  Joo Heung Kim aff001;  Hyun Ju Han aff003;  Yeon A. Choi aff003;  Ae Ran Choi aff003;  Joo Hyuk Sohn aff004;  Seung Il Kim aff001
Působiště autorů: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea aff001;  Department of Human Biology and Genomics, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea aff002;  Avison Biomedical Research Center, Yonsei University College of Medicine, Seoul, Korea aff003;  Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225082

Souhrn

Purpose

A patient-derived xenograft (PDX) model is an in vivo animal model which provides biological and genomic profiles similar to a primary tumor. The characterization of factors that influence the establishment of PDX is crucial. Furthermore, PDX models can provide a platform for chemosensitivity tests to evaluate the effectiveness of a target agent before applying it in clinical trials.

Methods

We implanted 83 cases of breast cancer into NOD.Cg-Prkdcscid Il2rgtm1Sug/Jic mice, to develop PDX models. Clinicopathological factors of primary tumors were reviewed to identify the factors affecting engraftment success rates. After the establishment of PDX models, we performed olaparib and carboplatin chemosensitivity tests. We used PDX models from triple-negative breast cancer (TNBC) with neoadjuvant chemotherapy and/or germline BRCA1 mutations in chemosensitivity tests.

Results

The univariate analyses (p<0.05) showed factors which were significantly associated with successful engraftment of PDX models include poor histologic grade, presence of BRCA mutation, aggressive diseases, and death. Factors which were independently associated with successful engraftment of PDX models on multivariate analyses include poor histologic grade and aggressive diseases status. In chemosensitivity tests, a PDX model with the BRCA1 L1780P mutation showed partial response to olaparib and complete response to carboplatin.

Conclusions

Successful engraftment of PDX models was significantly associated with aggressive diseases. Patients who have aggressive diseases status, large tumors, and poor histologic grade are ideal candidates for developing successful PDX models. Chemosensitivity tests using the PDX models provide additional information about alternative treatment strategies for residual TNBC after neoadjuvant chemotherapy.

Klíčová slova:

Breast cancer – Cancer chemotherapy – Cancer treatment – Drug research and development – Genetic causes of cancer – Histology – Mammalian genomics – Medical implants


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PLOS One


2019 Číslo 12