News

University of Rochester Medical Center scientists discovered new genetic evidence linking cholesterol and cancer, raising the possibility that cholesterol medications could be useful in the future for cancer prevention or to augment existing cancer treatment.

The data, published in the online journal Cell Reports, support several recent population-based studies that suggest individuals who take cholesterol-lowering drugs may have a reduced risk of cancer, and, conversely that individuals with the highest levels of cholesterol seem to have an elevated risk of cancer.

The cancer-cholesterol question has been debated since the early 20^th century, and along with it doctors and scientists have observed various trends and associations. However, until now genetic evidence directly linking cholesterol and malignancy has been lacking, said senior author Hartmut (Hucky) Land, Ph.D., Robert and Dorothy Markin Professor and chair of the Department of Biomedical Genetics and Professor in the department of Biochemistry & Biophysics, and director of research and co-director of the James P. Wilmot Cancer Center at URMC.

A new approach to finding genes important in the onset of cancer is described in Nature. The findings could help to identify new targets for tumor therapy.

Several genes, or oncogenes, cooperate with each other to transform normal cells into cancer cells. Hartmut Land and colleagues have now identified a list of other genes - termed cooperation response genes (CRGs) - that are regulated downstream of these oncogenes. By interfering with each CRG individually, the team were able to show that 14 out of 24 of them had a critical role in tumor formation. Restoring expression of these genes to the levels observed in normal cells prevented the formation of tumors. What's more, genetic perturbations of CRGs with relatively smaller effects when examined on their own show evidence of being essential when analyzed in combination.

The findings represent an important step in the search for the chink in the armor in human cancer - the elusive gene that cancer cells simply cannot live without.

Pinpointing new targets for cancer treatments is as difficult as finding a needle in a haystack, yet a University of Rochester team has discovered an entire novel class of genes they believe will lead to a greater understanding of cancer cell function and the next generation of effective and less harmful therapies for patients.

University of Rochester scientists, while investigating the two most frequent types of mutations in cancer, discovered a possible new route to treatment that would take advantage of the mutations instead of trying to repair them. The research is reported online this week in the journal Nature Structural & Molecular Biology.

In experiments with rodent and human cells, co-authors Mingxuan Xia, Ph.D., and Hartmut Land, Ph.D., explored how the Rho family of proteins, which are involved in cell movement, and thus in the progression from benign to malignant cancer, are controlled by two well-known cancer genes, p53 and Ras. By closing in on this deadly collaboration, researchers showed for the first time why some molecules such as Rho are targeted by cancer genes - and how they might lead to a promising way to intervene against cancer.

We have very little understanding of how Ras and p53 or any other potent gene mutations cooperate to cause malignant tumors, said Land, who is professor and chair of the Department of Biomedical Genetics and scientific director of the James P. Wilmot Cancer Center at the University of Rochester. But we have suspected for a long time that the way to develop rational searches for new drug targets is to first understand how these oncogenes cooperate. And in this study we’ve shown for the first time that this idea might work.