Utility of patient-derived lymphoblastoid cell lines as an ex vivo capecitabine sensitivity prediction model for breast cancer patients

Gladys Morrison, Divya Lenkala, Bonnie LaCroix, Dana Ziliak, Vandana Abramson, Phuong Khanh Morrow, Andres Forero, Catherine Van Poznak, Hope S. Rugo, Rita Nanda, Peter H. O'Donnell, R. Stephanie Huang

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Capecitabine is commonly used in treating breast cancer; however, therapeutic response varies among patients and there is no clinically validated model to predict individual outcomes. Here, we investigated whether drug sensitivity quantified in ex vivo patients' blood-derived cell lines can predict response to capecitabine in vivo. Lymphoblastoid cell lines (LCLs) were established from a cohort of metastatic breast cancer patients (n = 53) who were prospectively monitored during treatment with single agent capecitabine at 2000 mg/m2/day. LCLs were treated with increasing concentrations of 5'-DFUR, a major capecitabine metabolite, to assess patients' ex vivo sensitivity to this drug. Subsequently, ex vivo phenotype was compared to observed patient disease response and drug induced-toxicities. We acquired an independent cohort of breast cancer cell lines and LCLs derived from the same donors from ATCC, compared their sensitivity to 5'-DFUR. As seen in the patient population, we observed large interindividual variability in response to 5'-DFUR treatment in patient-derived LCLs. Patients whose LCLs were more sensitive to 5'-DFUR had a significantly longer median progression free survival (9-month vs 6-month, log rank p-value = 0.017). In addition, this significant positive correlation for 5'-DFUR sensitivity was replicated in an independent cohort of 8 breast cancer cell lines and LCLs derived from the same donor. Our data suggests that at least a portion of the individual sensitivity to capecitabine is shared between germline tissue and tumor tissue. It also supports the utility of patient-derived LCLs as a predictive model for capecitabine treatment efficacy in breast cancer patients.

Original languageEnglish (US)
Pages (from-to)38359-38366
Number of pages8
JournalOncotarget
Volume7
Issue number25
DOIs
StatePublished - 2016

Keywords

  • Breast cancer
  • Capecitabine
  • Ex vivo model
  • Lymphoblastoid cell lines
  • Patient-derived model

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    Morrison, G., Lenkala, D., LaCroix, B., Ziliak, D., Abramson, V., Morrow, P. K., Forero, A., Van Poznak, C., Rugo, H. S., Nanda, R., O'Donnell, P. H., & Huang, R. S. (2016). Utility of patient-derived lymphoblastoid cell lines as an ex vivo capecitabine sensitivity prediction model for breast cancer patients. Oncotarget, 7(25), 38359-38366. https://doi.org/10.18632/oncotarget.9521