Heat Shock Aids Cancer Treatment

The ONYX-015 mutated adenovirus replicates only in tumor cells, which become so filled with viral particles that they burst. However, treatment of cancer patients with the virus has not been as successful as expected. Investigators at the University of California, San Francisco (USA), examined why ONYX-015 did not undergo replication in some cancer cells, and how tumor cells could be made more responsive to ONYX-015 therapy.

As ONYX-015 lacks E1B-55K capability that includes p53 degradation, RNA export, and host protein shutoff, the host cancer cell must provide these functions. Resistant tumors were found to fail to provide the mechanism for RNA export, and the virus was unable to replicate. Results from the current study in the July 2005 issue of Cancer Cell showed that heat shock, induced either chemically or mechanically, restored the RNA export function, which allowed the virus to replicate and kill the cancer cell.

First author Dr. Clodagh C. O'Shea, an assistant researcher in the Cancer Research Institute of the University of California, San Francisco, said, "Our data suggest that a clinical strategy that does not advocate the use of pharmacological agents to suppress fever would favor the tumor-selective replication of ONYX-015. This study indicates that induction of a heat shock response by pharmacological agents (that could potentially be administered systemically) or local hyperthermia, could greatly augment and broaden ONYX-015's clinical utility as a cancer therapy.”



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