Introgen Therapeutics Inc has published the preclinical data from studies of INGN 241 in combination with radiotherapy in lung cancer cells, which shows INGN 241 enhances the cell killing effects of radiation in cancer cells but not in normal lung cells. This effect appears to be mediated by suppressing the repair of radiation-induced DNA damage.

"These data provide a direct molecular explanation for our previous observations that INGN 241 enhances the effects of radiotherapy in cancer cells," said Dr. Raymond E Meyn, chair (Ad Interim) of the Department of Experimental Radiation Oncology at M. D. Anderson. "This study complements our recent publication in Molecular Therapy demonstrating that INGN 241 can kill lung tumours in animals by blocking angiogenesis (tumour blood supply). Thus, the combinations of direct killing of tumour cells by blocking DNA repair and starving tumours of nutrients by anti-angiogenesis may synergize to provide enhanced anti-cancer activity. The results of these studies validate the use of INGN 241 in combination with radiotherapy for the treatment of non-small cell lung cancer, and other cancers," he added later.

The studies reported evaluated the impact of INGN 241 on a specific molecular pathway that is involved in repairing breaks in double-stranded DNA. These breaks are induced by radiation and are the primary mechanism through which radiotherapy kills cancer cells. The ability of cancer cells to repair these breaks may lead to resistance to radiotherapy. In these studies, the addition of INGN 241 to cultured lung cancer cells suppressed the expression of several genes involved in the repair pathway. This suppression was not observed in normal cells treated with INGN 241. Suppression of these genes in lung cancer cells resulted in decreased levels of DNA repair and enhanced cancer cell death after ionizing radiation. There was no significant reduction in DNA repair in normal cells treated with radiation and INGN 241.

"The ability of INGN 241 to elicit anti-cancer effects in cancer cells without impacting normal cells is one of the most exciting features of this product candidate," said Sunil Chada, Introgen's director of Research and Development. He added, "The major side effects associated with radiotherapy result from damage to normal cells and tissue. These new studies demonstrate that INGN 241 increases the cell killing effects of radiation in lung cancer cells, but not in normal lung cells. We hope that this will translate into improved tumour responses without an increase in side effects. Additionally, the addition of INGN 241 to radiotherapy may allow a therapeutic effect to be achieved at a lower dose of radiation, potentially reducing the treatment limiting side effects associated with radiotherapy."

The studies were conducted by researchers at The University of Texas M. D. Anderson Cancer Centre in conjunction with Introgen scientists, and the results appear in the current issue of Oncogene.