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Archive - Apr 26, 2012

Discovery of Small Molecules That Kill Cancers Caused by HPV

Researchers at The Wistar Institute in Philadelphia, Pennsylvania, have announced the discovery of small molecules that kill cancer cells caused by infection with human papillomavirus (HPV). Their results, in both cell and mouse models, demonstrate that the small molecule inhibitors protect a tumor-suppressing protein targeted by viral proteins, thus killing the infected tumor cells. The Wistar scientists presented their findings in the April 20, 2012 issue of Chemistry & Biology. The researchers believe that, with further testing and refinement, their inhibitors could provide a therapeutic for HPV-caused tumors, such as those seen in cervical cancer. “While there is an effective vaccine for preventing HPV infection, there is currently no therapeutic that specifically targets cancers caused by the virus,” said Ronen Marmorstein, Ph.D., senior author, Hilary Koprowski, M.D. Professor, and leader of The Wistar Institute Cancer Center’s Gene Expression and Regulation program. “HPV often turns cells cancerous for the virus’s own reproductive advantage, and we have found a class of small molecules that effectively prevents a key HPV protein from allowing cells to become cancerous,” Dr. Marmorstein said. “We think that this could be the start of an effective drug strategy for cancers caused by HPV.” HPV is one of the primary infectious causes of cancer, responsible for most cases of cervical cancer, nearly 20 percent of all head and neck cancers, and has been implicated in cancers of the vagina, penis, and anus. American Cancer Society statistics estimate that over 4,000 women will die this year from cervical cancer alone. The U.S. Centers for Disease Control estimate that about 50 percent of sexually active men and women will be infected with HPV at one point in their lives.

Advanced Pancreatic Tumors Depend on Continued Oncogene Activity

Researchers at the Dana-Farber Cancer Institute have shown that advanced pancreatic cancers in mice cannot survive without continued expression of a mutant oncogene that "rewires" key metabolic pathways to fuel the cancer cells. The findings, published in the April 27, 2012 issue of Cell, suggest that some of these altered metabolic pathways might be potential targets for future drugs to treat the deadly cancer. The investigators report that when they experimentally shut down the expression of the Kras oncogene in mice, the pancreatic tumors rapidly shrank, and, in some cases, left no visible signs of cancer. This outcome, they said, provides evidence that advanced pancreatic cancers are "addicted" to the Kras oncogene for their continued growth. "This experiment allowed us to demonstrate that pancreatic cancers in their native setting are dependent on continued oncogenic Kras expression for tumor maintenance," says Alec Kimmelman, M.D., Ph.D., co-corresponding author of the report along with Ronald DePinho, M.D., formerly at Dana-Farber and now at M.D. Anderson Cancer Center in Houston. Dr. Kimmelman said they also discovered that oncogenic Kras "basically reprograms the glucose metabolism of the cell by regulating the expression of key metabolic enzymes, some of which might provide novel therapeutic targets." If that is the case, then attacking these pathways might be more feasible than attempting to block KRAS directly, since KRAS has proven frustratingly difficult to hit with designer drugs. It is estimated that pancreatic ductal adenocarcinoma will be diagnosed in more than 43,000 people in the United States in 2012, according to the American Cancer Society, and more than 37,300 will die from the disease, which has a 5-year survival rate of only 5 percent.