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A new drug combination tested in mice may target the cells responsible for driving some pancreatic tumors. The combination of gemcitabine and the experimental drug tigatuzumab eliminated populations of cancer stem cells and reduced tumor growth in a mouse model of pancreatic cancer, researchers from the Johns Hopkins Sidney Kimmel Cancer Center reported at the AACR annual meeting.
The results provide a rationale for testing the promising combination in patients with this deadly disease, Dr. Rajesh Kumar NV and his colleagues concluded.
Cancer stem cells are thought to self renew while giving rise to tumors, and they may resist conventional treatments. The researchers found that human pancreatic cancer stem cells overexpress a protein called death receptor-5 (DR-5), which is involved in programmed cell death (apoptosis). The protein is also the target of tigatuzumab, a humanized monoclonal antibody also known as CS-1008.
To evaluate the drug’s effects on these important cells, mice were given tigatuzumab alone, gemcitabine alone, or a combination. Although gemcitabine reduced tumor size, it increased levels of pancreatic cancer stem cells (as defined by the protein markers ALDH, CD24, and CD44), and all of the tumors recurred. The combination treatment, however, led to long-term remissions in half of the treated mice.
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