BOSTON--Researchers at Dana-Farber Cancer Institute have demonstrated a molecular strategy they say could make a much larger variety of tumors treatable with PARP inhibitors, a promising new class of cancer drugs.
Currently, the role of PARP inhibitors has mainly been restricted to cancers whose cells lack functioning versions of the damage-repair proteins BRCA1 or BRCA2 -- chiefly certain breast and ovarian cancers.
In a paper published online by Nature Medicine, Geoffrey Shapiro, MD, and colleagues report that the BRCA1 repair protein is dependent on another protein, CDK1, known primarily as a regulator of the cell division cycle. When the scientists blocked CDK1 in cancer cell lines and in a mouse model of lung cancer, BRCA1 function was disrupted, making them susceptible to being killed by a PARP inhibitor.
Because most types of tumors don't have a mutated BRCA1 protein, they are less likely to be affected by PARP inhibitor treatment. The new findings, said Shapiro, "suggest that by blocking CDK1, we can disable BRCA1 in many types of cancers and make them sensitive to a PARP inhibitor. It could extend the use of these drugs to a much larger group of patients."
Shapiro, who heads Dana-Farber's Early Drug Development Center, said a clinical trial combining a CDK1 blocker and a PARP inhibitor in a variety of solid tumors is being planned.
Cells are equipped to heal damage to their DNA strands, which are constantly being nicked or broken by exposure to environmental contaminants or randomly during cell division. Cancer cells, in addition, become adept at repairing potentially lethal DNA damage caused by radiation and chemotherapy drugs, and use their DNA repair machinery to survive and grow uncontrollably.
A major thrust in cancer research currently is developing ways to disable tumor cells' repair toolkits to make them more vulnerable to DNA-damaging agents. PARP inhibitor drugs prevent tumor cells from
|Contact: Bill Schaller|
Dana-Farber Cancer Institute