Research in Alik Honigman
The ongoing of generation of hypoxic regions is a unique property of solid tumors. These regions are resistant to chemotherapy and radiation and thus present a major obstacle in the treatment of solid tumors. We have found that CREB and Hif1 play a major role in the survival of tumor cells at hypoxia in vitro and tumor progression in vivo.
The retrovirus MuLV replicate only in propagating cells thus it has a preference to tumor cells. We inserted shRNA targeting CREB and/or HIF1 keeping the replication competence of the virus. The combination of knockdown of these two hypoxia response regulators and the limitation of the replication competent MuLV vectors target specifically solid tumors. We found that knockdown of CREB or Hif1 sensitize several tumor cells to chemotherapeutic agents allowing treatment of the tumors with diminished concentrations of the chemotherapy and thus the combinatorial treatment decrease side effects of the treatment and abrogation to tumor progression.