Activation of dsRNA dependent protein kinase PKR in Karpas299 does not lead to cell death.

Activated double-stranded RNA (dsRNA)-dependent protein kinase PKR is a potent growth inhibitory protein that is primarily activated in virally infected cells, inducing them to die. We have recently shown that PKR can be selectively activated in cancer cells, by in situ generation of dsRNA following introduction of antisense RNA complementary to an RNA expressed specifically in the cancer cell. The feasibility of this approach was demonstrated using a glioblastoma line that overexpresses a truncated form of the EGFR.

A cellular screening assay to test the ability of PKR to induce cell death in mammalian cells.

Long double-stranded RNA (>30 bp), usually expressed in cells infected with RNA viruses, triggers antiviral responses that induce apoptosis of the infected cells. PKR can be selectively activated in glioblastoma cells by in situ generation of dsRNA following introduction of antisense RNA complementary to an RNA expressed specifically in these cells. Harnessing PKR for the selective killing of cancer cells is potentially a powerful strategy for treating cancer, but we were unable to induce apoptosis by this approach in a T cell lymphoma.

RNA molecules as anti-cancer agents.

The inhibition of cancer growth and progression is one of the major challenges facing modern medicine. Despite significant progress in the development of therapies against cancer, only in a few cases are these therapies effective. Because cancer is a complex disease, agents that target a single oncogenic pathway have low efficacy, in addition to allowing the emergence of drug resistance.

Tumor specific activation of PKR as a non-toxic modality of cancer treatment.

Over the past decade progress has been made in the development of therapies against cancer. Small molecules, mainly tyrosine kinase inhibitors (tyrphostins) like Gleevec, Iressa targeting CML and EGFR overexpressing tumors have entered the clinic, where a large number of other tyrphostins are at various stages of clinical development. In parallel a few antibodies like Herceptin targeting breast cancer overexpressing Her-2 and Rituxan targeting B cell malignancies are utilized in the clinic.