Some new laboratory research bodes potentially well for the crop of Notch inhibitor anti-cancer drugs now under development.
In a nutshell: Scientists in the U.S., China and elsewhere have figured out a complex process in which three molecular networks interconnect, and the chain reaction can lead to tumor development. Details are in the latest Molecular Cell.
One of those networks involves a Notch-1 receptor, so the added knowledge could help fine-tune Notch inhibitor drugs now being developed by companies such as Merck ($MRK) and Eli Lilly ($LLY), the researchers say. But in conditions such as liver cancer, where all three molecular networks appear to express themselves, scientists will have new drug targets to treat and possibly even prevent various cancers.
Mien-Chie Hung, vice president for basic research at The University of Texas MD Anderson Cancer Center, led the study, which focused on liver cancer cell lines. Scientists determined that in these cells TNFa (tumor necrosis factor alpha) activates IKK alpha, a protein kinase that promotes inflammation and regulates other proteins. IKKa, in turn, moves into the cell nucleus where it distorts the FOXA2 transcription factor. When working properly, FOXA2 triggers the NUMB tumor suppressor, which in turn blocks NICD, an activated part of Notch-1 that can cause genes to turn cells cancerous. But, when FOXA2 is disabled, it doesn't activate NUMB. Notch-1 can then activate and cause cancer to develop, the researchers note.
The scientists plan to test their molecular network chain in animal models, followed by human clinical trials if they succeed. Funding came from a variety of sources, including the National Cancer Institute, the National Science Council of Taiwan and The MD Anderson-China Medical University and Hospital Sister Institution Fund.
- here's the release
- read the journal abstract
Notch inhibitors may offer breakthrough on brain cancer
Anti-Notch1 mAb demonstrates potent inhibitory activity