In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e14694-e14694
Abstract:
e14694 Background: Generation of patient-derived models for breast cancer has been difficult. In other histologies, success was higher in refractory disease. With the goal to develop a protean resource for testing novel compounds and combinations for treatment refractory breast cancer, we establish patient-derived murine xenograft models (PDX) from tumors clinically unresponsive to at least anthracyclin, platin and taxane. Here we report phenotypic and drug testing data of our established breast cancer models. Methods: On immunodeficient NOG mice, PDX were engrafted from breast cancer tissue samples. The tissues were obtained from patients with disease progression after chemotherapy with three to four drugs. The established PDX were characterized by immunohistochemistry and the PDX and primary tumor are currently undergoing exome and transcriptome sequencing. The PDX were tested for response to all standard chemotherapy agents. The drug testing included platin, taxane, anthracycline, 5-FU, Everolimus, Eribulin and depending on the subtype tamoxifen, olaparib, and a CDK4/6 Inhibitor. Results: Since May 2017 30 breast cancer samples have been processed under rapid and stringent conditions. Currently five models, three TNBC and two hormone receptor positive PDX, have been fully engrafted, phenotypically compared and drug tested. The immunohistochemistry (estrogen/progesterone/androgen/Her2 receptor, Ki-67, CK5/6) of original tumor and PDX were correlative. All patients had shown clinical resistance to platin, anthracyclines, and taxanes in the neoadjuvant or palliative setting. Concordant with the clinical resistance, the PDX models showed only limited or transient sensitivity to single agents. Six more PDX, three TNBC, two HR+ and one Her2+, are currently in various states of engraftment and testing. Conclusions: With our stringent approach, we successfully generated PDX models in 15%, which may rise to 30% with the ongoing models. Phenotype between patient tumors and PDX was consistent. The minor differences in responsiveness to chemotherapy may be due to differences in stromal factors. In summary, the PDX of refractory tumors are a versatile resource for preclinical studies of novel treatment approaches.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.15_suppl.e14694
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2019
detail.hit.zdb_id:
2005181-5
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