Heat shock improves viral cancer therapy
(7 August 2005: VIDYYA MEDICAL NEWS SERVICE) -- Resistance to treatment with ONYX-015, a genetically modified virus that selectively attacks tumor cells, can be overcome by inducing a heat-shock response in tumor cells, according to a study in the July Cancer Cell.
ONYX-015, the first modified adenovirus to be approved for testing in human clinical trials, has proven in early stage clinical trials to be effective in shrinking tumors when combined with chemotherapy. The researchers sought to determine why some patients failed to respond to treatment with ONYX-015.
Dr. Clodagh O'Shea and colleagues at the University of California, San Francisco, reported that in laboratory studies, inducing a heat-shock response made tumor cells that were initially resistant to therapy with ONYX-015 amenable to treatment. The heat shock, the authors noted, "rescued" intracellular functions needed for the virus to replicate inside the tumor cell and induce cell death.
Specifically, they reported, heat shock restores late RNA export in resistant cells. The heat-shock response was induced both by pharmacologic induction with benzoquinoid ansamycins and by incubating the cells at elevated temperatures. In both cases, late RNA functions were rescued in resistant tumors, increasing viral yield 10-fold or more in 8 out of 10 resistant tumor cell lines. Moreover, viral activity in primary cells was not restored by the heat shock.
A clinical strategy that does not advocate suppression of fever, or that includes the heat-shock induction, they concluded, "could greatly augment ONYX-015's clinical utility as a cancer therapy."
Return to Vidyya Medical News Service for 7 August 2005