Although the German pathologist Rudolf Virchow discovered 150 years ago an association between chronic inflammation and cancer, its molecular basis has eluded scientists. Using his own designed sophisticated mouse models, Dr. Ben-Neriah has shown that the activation of the protein complex NF-kB mediates the pro-tumorigenic activity of inflammation and that in the absence of this signal, the premalignant cells die and tumor initiation fails.
Chronic inflammation however is only blamed for driving roughly 15-20% of the human tumors, but it was shown that non-steroidal anti-inflammatory drugs (NSAIDs) are effective in reducing the cancer incidence and mortality of many tumor types that are not associated with chronic inflammation. Again, with the use of animal models engineered in his lab, Dr. Ben-Neriah was able to detect a new type of low grade inflammatory phenomenon dubbed "parainflammation, having distinct gene and protein expression signature even in the absence of tissue infiltrating cells. Ben-Neriah found that parainflammation is a widespread phenomenon non-concordant with canonical inflammation affecting more than 30 percent of the major cancer types. This type of inflammation is suppressed by NSAID treatment, and may account for the remarkable effects of NSAIDs in preventing cancer development.
More recently, the Ben-Neriah lab has made another fundamental discovery, showing that one of the major roles of the tumor suppressor protein, p53 in colorectal cancer is in preventing epithelial cell invasion. The new invasive gene signature recognized by Ben-Neriah and colleagues might therefore be useful for identifying early signs of malignancy.
In addition to achievements in basic biomedical research, Prof. Ben-Neriah has made major contributions to translational medicine. The first effective Bcr-Abl inhibitors that eliminate Philadelphia-positive chronic myelogenous leukemia (CML) cells were collaboratively developed by Ben-Neriah and Dr. Alex Levitzki. These studies paved the way for the future development of the successful drug Gleevec. Another class of inhibitors directed at the kinase CKI are being developed in his laboratory as a new type of chemotherapy highly effective against acute leukemia.