Reovirus Therapy May Optimize the Efficacy of Irinotecan in Colorectal Cancer

Online, May 25, 2010 (Newswire.com) - There may be new hope for colorectal cancer patients who fail on first-line drug combinations harnessed against tumors that harbor a mutation in the kras oncogene. Currently, for these patients, the only option after failure of first-line therapy is irinotecan or drug cocktails containing irinotecan (FOLFIRI Researchers from the Montefiore Medical Center have discovered that using a cancer biologic agent made from the human reovirus may offer a new hope for these patients.

Irinotecan is a chemotherapy drug made from a type of plant alkaloid known as a topoisomerase I inhibitor. It is thought to work by blocking the action of an enzyme in cells called topoisomerase I.

Cells need this enzyme to keep their DNA in the proper shape when they are dividing into two cells. Blocking this enzyme leads to breaks in the DNA, which leads to cell death. Because cancer cells divide faster than normal cells, they are more likely than normal cells to be affected by irinotecan.

Calgary-based Oncolytics Biotech Inc. has developed an innovative approach to cancer therapy that relies on viruses. Specifically, Oncolytics is testing a biologic called REOLYSIN®, which is derived from the human reovirus.

"One of the distinguishing characteristics of the reovirus is its tendency to replicate within certain cancer cells, namely, those that possess a feature known as an activated Ras pathway," said Brad Thompson, Chairman, President and Chief Executive Officer of Oncolytics Biotech. "Approximately two-thirds of all cancers involve cells that are Ras-activated. REOLYSIN appears to kill off these cancer cells by rupturing their walls, creating a chain reaction of 'explosions' that rip through tumors. So far, when used in combination with chemotherapy, it proves a one-two punch to tumors."

Dr. Raviraja Seetharam and his research team at Montefiore recently presented a poster, titled "The addition of REOLYSIN, an oncolytic reovirus, to irinotecan shows synergistic anticancer activity in colorectal cancer cell lines," that covered research done in vitro regarding a novel therapeutic approach for treating patients with colorectal cancer tumors that harbor a mutation in the kras oncogene and who have have failed first-line therapy.
The study concluded that REOLYSIN and irinotecan as single agents were cytotoxic to all colon cell lines studied. Further, when REOLYSIN was combined with irinotecan, there was evidence of synergistic cytotoxicity in seven of eight tested cell lines. The researchers concluded that the combination of REOLYSIN and irinotecan is synergistic in colorectal cancer cell lines, including those with kras mutations, and is worthy of exploration in human patients.