A Triple-negative Matrix-producing Breast Carcinoma Patient-derived Orthotopic Xenograft (PDOX) Mouse Model Is Sensitive to Bevacizumab and Vinorelbine, Regressed by Eribulin and Resistant to Olaparib

Abstract

Background/Aim: Matrix-producing breast carcinoma (MPBC) is a rare and usually aggressive triplenegative breast cancer (TNBC). In this study, we determined drug sensitivity for a triple-negative MPBC, without BRCA mutations, in a patient-derived orthotopic xenograft (PDOX) model. Materials and Methods: The MPBC PDOX model was established in the left 2 nd mammary gland of nude mouse by implantation of the patient tumor using surgical orthotopic implantation (SOI). We randomized MPBC PDOX mice into 5 groups (n=5 mice/per treatment group) when the tumor volume reached 80 mm 3 : G1, control-no treatment; G2, bevacizumab [intra-peritoneal (i.p.), weekly, for 2 weeks]; G3, vinorelbine (i.p., weekly, for 2 weeks); G4, olaparib (oral., daily, for 2 weeks); G5, eribulin [intravenous (i.v.), weekly, for 2 weeks]. The mice in each treatment group were sacrificed on day 15. Tumor volume and body weight were measured once/week. Results: The MPBC PDOX model was resistant to olaparib (p=0.22). The MPBC PDOX model treated with bevacizumab and vinorelbine showed significantly suppressed tumor growth compared to the untreated group (p=0.005 and 0.002, respectively). However, only eribulin regressed the tumor (p=0.0001). Eribulin was more effective than olaparib (p=0.0001), bevacizumab (p=0.0025) and vinorelbine (p=0.0061). Conclusion: Eribulin has clinical potential as treatment for triple-negative MPBC patients that are resistant to a PARP inhibitor such as olaparib.Triple-negative breast cancer (TNBC) lacks expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) protein.Approximately 15 to 20% of all breast cancers are TNBC (1, 2). TNBC is a highly aggressive breast cancer with frequent recurrence and metastasis, and a higher mortality rate compared to other types of breast cancer (3). Furthermore, the 2509

Co-implantation of Tumor and Extensive Surrounding Tissue Improved the Establishment Rate of Surgical Specimens of Human-Patient Cancer in Nude Mice: Toward the Goal of Universal Individualized Cancer Therapy

“…The future goal is to use the new method of patient-tumor transplantation to enable universal individualized therapy for cancer patients, such that each cancer patient has their own mouse tumor model to help identify improved therapy. The results of the present study show that high tumor stage and the presence of metastasis in the patient increased the probability of tumor engraftment in nude mice, suggesting that the patients in greatest need will have the best chance for identification of more effective therapy with a mouse model of their tumor, especially the PDOX model, which mimics the patient (4,(12)(13)(14)(15)(16).…”

“…Individualized cancer therapy currently uses genome analysis (5), drug-sensitivity testing with 3-D culture of tumor in vivo 34: 3241-3245 (2020) fragments (6)(7)(8)(9) or organoids (10,11) as well as patientderived xenograft (PDX) or, patient-derived orthotopic xenograft (PDOX) models (12)(13)(14)(15)(16). Genome analysis has helped only a limited number of cancer patients identify effective drugs (17).…”

A triple-negative matrix-producing breast carcinoma is arrested by tumor-targetingSalmonella typhimuriumA1-R in a PDOX model

“…Therefore, novel effective therapy is urgently needed for MPBC patients. Our previous studies of triplenegative MPBC PDOX, showed eribulin was effective (12,13).…”

“…We have previously demonstrated that the PDOX model retains the histopathological/molecular and metastatic characteristics of the original tumor after SOI in 5 mice (9-11). We previously showed eribulin regressed triple-negative MPBC PDOX mouse models (12,13).…”

Effects of Cancer Stem Cells in Triple-Negative Breast Cancer and Brain Metastasis: Challenges and Solutions

“…Recent developments in the patient derived xenograft (PDX) model seem capable of producing samples that are authentic to the host tumor, which replicate tumor growth, tumor diversity, and tumor progression, including metastatic potential [ 171 ]. Furthermore, in patients with TNBC, several applications of PDX models have been made in terms of drug screening [ 172 , 173 , 174 , 175 , 176 ], drug resistance profiling [ 177 ], prognostic and functional gene assessment [ 178 , 179 ], and metastatic assessment [ 180 , 181 ]. In the future, PDX models may become the trend in personalized therapy and minimize the need for expensive and prolonged randomized controlled trials.…”