Cancer is a disease of dysfunctional genes. Normal cellular genes that regulate cell
proliferation develop carcinogen-induced, or rarely, germline mutations that alter
the gene product so that it is permanently in an active configuration. Examples
include the Kras oncogene and the epidermal growth factor receptor. These oncogenes
confer the property of unlimited replication to cancer cells. Genes that normally
suppress cell growth or induce programmed cell death, after sensing DNA
damage, develop inactivating mutations in the cancer cell. Examples include the
p53 tumor suppressor gene and the retinoblastoma gene. Inactivation of these tumor
suppressor genes removes essential growth control mechanisms from the cell.
Strategies for replacing inactivated tumor suppressor genes or inactivating oncogenes
are logical extensions of the gene therapy concept. Investigators have been
pursuing these concepts for almost 20 years, but slow progress in developing systemic
delivery vehicles for genes and the ability to target tumors, and fragmentary
knowledge of the critical genes to target, have limited progress. Recently, significant
progress in sequencing the cancer genome, combined with advances in personalized
cancer treatment has converged to accelerate the development of cancer gene
therapy. Personalized or targeted cancer treatments rely on high throughput technologies,
including DNA sequencing, expression arrays, and proteomics to identify
critical pathways for cancer cell survival. Small molecule drug libraries are used to
identify drugs that may specifically inhibit a pathway.