About half of all cancer patients have a mutation in a gene called p53 which allows tumors to survive and continue growing even after chemotherapy has severely damaged their DNA. A new study by MIT biologists has found that tumor cells with mutated p53 can be made much more vulnerable to chemotherapy by blocking another gene called MK2. In a study of mice, tumors lacking both p53 and MK2 shrank dramatically when treated with the drug cisplatin, while tumors with functional MK2 kept growing after treatment.
P53 is a tumor-suppressor protein that controls cell division. Before cell division begins, p53 checks the cell's DNA and initiates repair, if necessary. If DNA damage is too extensive, p53 forces the cell to undergo programmed cell death, or apoptosis. Tumors that lack p53 can avoid this fate.
The findings suggest that giving cancer patients a combination of a DNA-damaging drug and an MK2 inhibitor could be very effective, says Michael Yaffe, MD, PhD, senior author of a paper describing the research published in the journal Cell Reports. Several drugs that inhibit MK2 are now in clinical trials to treat inflammatory diseases such as arthritis and colitis, but the drugs have never been tested as possible cancer treatments.
The potential combination of cisplatin and MK2 inhibitors is unlike other chemotherapy combinations that have been approved by the Food and Drug Administration, which consist of pairs of drugs that each show benefit on their own. “What we found is a combination that you would never have arrived at otherwise,” Yaffe says. “It's a non-obvious combination.” Read the article.
