Tumor-Targeting Salmonella typhimurium A1-R Sensitizes Melanoma With a BRAF-V600E Mutation to Vemurafenib in a Patient-Derived Orthotopic Xenograft (PDOX) Nude Mouse Model

Kei Kawaguchi, Kentaro Igarashi, Takashi Murakami, Ming Zhao, Yong Zhang, Bartosz Chmielowski, Tasuku Kiyuna, Scott D. Nelson, Tara A. Russell, Sarah M. Dry, Yunfeng Li, Michiaki Unno, Fritz C. Eilber, Robert M. Hoffman

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50 Citations (Scopus)

Abstract

Previously, a BRAF-V600E-mutant melanoma obtained from the right chest wall of a patient was grown orthotopically in the right chest wall of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. Trametinib (TRA), an MEK inhibitor, caused tumor regression. In contrast, another MEK inhibitor, cobimetinib (COB) could slow but not arrest growth or cause regression of the melanoma PDOX. First-line therapy temozolomide (TEM) could slow but not arrest tumor growth or cause regression. In addition, vemurafenib (VEM) was not effective even though VEM is supposed to target the BRAF-V600E mutation. We also previously demonstrated that tumor-targeting with S. typhimurium A1-R combined with TEM was significantly more effective than either S. typhimurium A1-R alone or TEM alone on the melanoma PDOX with the BRAF-V600E mutation. The present study used this PDOX model of melanoma to test its sensitivity to VEM combined with S. typhimurium A1-R compared to VEM alone and VEM combined with COB. VEM combined with S. typhimurium A1-R was significantly more effective than VEM alone or VEM combined with COB (P = 0.0216) which is currently first line therapy for advanced melanoma with a BRAF-V600E mutation. J. Cell. Biochem. 118: 2314–2319, 2017.

Original languageEnglish
Pages (from-to)2314-2319
Number of pages6
JournalJournal of Cellular Biochemistry
Volume118
Issue number8
DOIs
Publication statusPublished - 2017 Aug 1

Keywords

  • COBIMETINIB
  • COMBINATION THERAPY
  • DRUG-RESPONSE
  • MELANOMA
  • NUDE MICE
  • ORTHOTOPIC
  • PDOX
  • PRECISION MEDICINE
  • Salmonella typhimurium A1-R
  • TUMOR REGRESSION
  • VEMURAFENIB

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Kawaguchi, K., Igarashi, K., Murakami, T., Zhao, M., Zhang, Y., Chmielowski, B., Kiyuna, T., Nelson, S. D., Russell, T. A., Dry, S. M., Li, Y., Unno, M., Eilber, F. C., & Hoffman, R. M. (2017). Tumor-Targeting Salmonella typhimurium A1-R Sensitizes Melanoma With a BRAF-V600E Mutation to Vemurafenib in a Patient-Derived Orthotopic Xenograft (PDOX) Nude Mouse Model. Journal of Cellular Biochemistry, 118(8), 2314-2319. https://doi.org/10.1002/jcb.25886