Selective Oncolytic Therapy for Hypoxic Breast Cancer Cells

摘要

We tested the hypothesis that hypoxic breast cancer cells would be more permissive to herpes simplex (HSV-1)-derived plasmids. Since hypoxic cells are more resistant to traditional therapies this work could provide a new strategy for treating aggressive breast cancer. The general hypothesis was that ERK (extracellular receptor kinase) would be active in hypoxic cells rendering them susceptible to oncolytic viruses such as R3616. R3616 lacks the gamma-1 34.5 gene that normally blocks the host cells attempt to inhibit viral protein synthesis. We determined whether hypoxic MCF-7 MDA-MB-231 and MDA-MB-435 cells would be more permissive to R3616. We observed that hypoxic MDA-MB-231 cells were indeed more permissive to R3616; however MDA-MB-435 cells were not. This observation may lead to future experiments to identify novel treatment modalities for hypoxic cells. However considering that ERK1/2 activation is constitutive in MDA-MB-231 cells, it is possible that other hypoxic signaling pathways are important in rendering the MDA-MB-231 cells permissive to the oncolytic virus.