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

English version

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
prolekare.web.journal.doi_sk: https://doi.org/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:

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

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