Terminal metastatic cancer effectively treated in mice

Oct 5 2010

Terminal metastatic cancer - the presently untreatable cause of the great majority of all cancer deaths - has now been effectively treated in three common fatal cancers in mice, announced Genomic Systems, citing research published online today in the Proceedings of the National Academy of Science (PNAS).

“To be able to offer my patients with advanced cancers only palliative care and referral to hospice was not why I chose to become a cancer doctor. The profound, unmet medical and human needs of my patients in the terminal stages of cancer drove me into research.”

Research conducted by Robert J. Debs, M.D., senior scientist at the California Pacific Medical Center Research Institute in collaboration with four other laboratories has shown that a monoclonal antibody targeting a protein called PECAM-1 is effective against this now invariably lethal stage of cancer in mice. This antibody also treats less advanced cancers, as well as the debilitating wasting syndrome that can develop as cancers progress.

Anti-PECAM-1-antibody produces its anti-cancer effects not by binding to tumor cells, but rather by binding to PECAM-1 on the surface of normal endothelial cells that line blood vessels. Because it acts through normal cells rather than directly on cancer cells, it is effective against a variety of different cancer types.

Laboratory testing has now shown anti-PECAM-1-antibody to be effective against colon cancer, breast cancer and melanoma. These are among the most frequently diagnosed fatal cancers in the United States, according to the National Cancer Institute.

"For the first time, preclinical studies provide hope for patients and their physicians that even the terminal stages of cancer do not invariably represent a hopeless situation. Our research has shown that some terminal cancers, as well as the debilitating wasting syndrome that can accompany them can now be treated in mice," said Dr. Debs. "Hopefully, these studies will encourage increased interest in studying terminal cancers, as well as stimulate others to develop additional new therapies that effectively target this most devastating stage of cancer."

The research also indicates that this antibody is well tolerated, even when administered at high doses to mice already debilitated by very advanced metastatic cancers. The antibody appears to work by selectively blocking PECAM-1's regulation of secreted proteins that promote advanced cancer's now lethal growth. Dr. Debs believes that specifically targeting these growth-promoting factors themselves may further improve the treatment of terminal cancer, and has the potential to significantly improve the lives of patients now suffering hopelessly from it.

"Preclinical studies focusing on terminal cancer are rare. Therefore, these patients have no therapies to either treat their cancer or give them hope. As a cancer specialist, all I could do for my patients with terminal cancers was to help make their remaining days as comfortable as possible," said Dr. Debs, who is trained as a medical oncologist and hematologist. "To be able to offer my patients with advanced cancers only palliative care and referral to hospice was not why I chose to become a cancer doctor. The profound, unmet medical and human needs of my patients in the terminal stages of cancer drove me into research."

Genomic Systems is working to develop Phase 1 testing of anti-PECAM-1 monoclonal antibody in patients with advanced cancers, hopefully within 2 years.