Pancreatic cancer remains one of the deadliest cancers, but researchers may have found a combination therapy to reduce cancer stem cells and stop pancreatic cancer growth. Results will be presented at the American Association for Cancer Research 100th Annual Meeting 2009.
Rajesh Kumar N.V., Ph.D., a faculty member at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, said a combination therapy using tigatuzumab, a novel humanized death receptor-5 (DR-5) agonist antibody, along with gemcitabine, may result in reducing pancreatic cancer stem cells to achieve tumor remission and prevent tumor recurrence.
"Many advanced cancers, including pancreatic cancer, recur and result in patient death despite the use of chemotherapeutic and radiation modalities that initially lead to therapeutic responses," said Kumar. "A growing body of evidence supports the concept that cancer stem cells are the seeds of the most clinically deadly form of therapy-resistant human cancers. Emerging studies show that cancer stem cells are indeed more resistant to therapy than other cancer cells and might be the reason why conventional chemotherapy, while reducing tumor size, does not result in long-term cures."
Kumar and colleagues analyzed the cancer stem cells in ten patient-derived tumors implanted in laboratory mice and found that DR-5 is enriched in cancer stem cells compared to non-stem cell tumor populations. These mice either received tigatuzumab alone; gemcitabine, the current clinical treatment for pancreatic cancer; or a combination of the two agents.
They found that treatment with gemcitabine alone reduced tumor size, but the tumor cells that remained were rich in pancreatic cancer stem cells. In nearly all cases, the tumors returned.
However, treatment with gemcitabine and tigatuzumab resulted in the reduction of pancreatic cancer stem cells, caused tumor remission, and significantly increased time-to-tumor progression in 50 percent of treated cases from a median of 54 days to 103 days.
From a clinical standpoint, targeting cancer-sustaining pancreatic cancer stem cells will be of paramount significance since there are few effective therapies for pancreatic cancer and most of the patients die within the first year of diagnosis. "Clinically, this discovery could transform the way in which pancreatic cancer is treated and contribute towards making pancreatic cancer a more manageable disease," said Kumar.
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