Researchers at The University of Texas MD Anderson Cancer Center have found a protein, PKM2, that could act as a biomarker in patients with glioblastoma multiforme and have found a new role for a type of kinase inhibitor not tested in this condition so far. Glioblastoma multiforme is the most common and most dangerous form of brain cancer.
PKM2 works by kicking off cell division and by boosting the processing of glucose into energy (the Warburg effect), both of which promote cell growth. PKM2 is naturally active in small children, and it then gets turned off when it's no longer needed. However, in many types of cancer, it gets turned back on and increases the rate of cell division in the cancer. To do all this, it has to get inside the cell.
"PKM2 must get to the nucleus to activate genes involved in cell proliferation and the Warburg effect," Dr. Zhimin Lu of MD Anderson's Department of Neuro-Oncology said in a press release. "If we can keep it out of the nucleus, we can block both of those cancer-promoting pathways. PKM2 could be an Achilles' heel for cancer."
Kinase inhibitors are used to treat cancer and inflammation, and a certain type, the MEK/ERK inhibitors, stopped PKM2 from getting into the nucleus. In mice, the MEK inhibitor selumetinib inhibited tumor growth. The results were published in Nature Cell Biology.
Array BioPharma's ($ARRY) selumetinib is in Phase II development in collaboration with AstraZeneca ($AZN) for cancer, including non-small cell lung cancer. This type of drug has not yet been tried in glioblastoma multiforme, according to the researchers, and PKM2 could be used as a biomarker to pick out those patients most likely to respond.
- read the press release
- see the abstract