Adenoviral Vectors for Cancer Gene Therapy
Prem Seth, Yu Katayose, and Amol N.S. Rakkar
Cancer can be considered a “genetic” disorder, and thus a legitimate target for gene therapy, in as much as it arises as a result of a stepwise accumulation of genetic defects in a clone of cells. In the last decade or so, several epigenetic and genetic events have been characterized that contribute to tumor initiation, progression, and metastasis. It is now well understood that gain of a dominant oncogene such as ras mutation, or loss of a tumor suppressor gene such as p53 can induce an uninhibited cell growth leading to tumorigenesis. In addition, the failure of the immune system to recognize and eliminate the tumor cells allows the cancer cells to proliferate and accumulate further genetic defects. Other contributors to tumor progression include tumor generated factors that enhance angiogenesis, such as vascular endothelial derived growth factor (VEGF), and alterations in expression of adhesion molecules in the cancer cells that allow the cancerous cells to dislodge from their primary microenvironment and metastasize to distant sites.