Researchers have found a possible new way to treat cancer by exploiting a biological weakness in the most commonly mutated gene believed to be involved in human cancers.
The mutant gene, K-Ras, is thought to be the culprit behind more than a third of all cancers, including colon, lung and a majority of pancreatic cancers. Ras cancers are considered "undruggable" because previous attempts to halt their growth have failed.
But investigators at NYU Langone Medical Center showed in experiments in human cancer cells that K-Ras tumor cells' constant need to check and mend their DNA plays a major role in tumor growth. DNA wear and tear happens routinely, from factors like stress or ultraviolet radiation. In order for cell division and growth to occur, DNA has to repair itself. In cancer cells, DNA damage is accelerated.
In a study published in Cancer Cell, researchers found that blocking K-Ras cancer cells' ability to "check" their DNA made a commonly used chemotherapy drug more effective at killing tumor cells. Scientists did this by switching off the activity of two related genes, H-Ras and N-Ras.
"Our finding suggests that K-Ras cancers can be made more susceptible to existing therapies by interfering with their DNA repair mechanisms," senior study investigator Dafna Bar-Sagi said in a statement. Bar-Sagi is the senior vice president and vice dean for science, and chief scientific officer of the NYU Langone Medical Center.
Elda Grabocka, senior study author, said the ultimate goal is to "map out" the Ras signaling pathways and to identify as many therapeutic drug targets as possible.
- read the press release
- see the study abstract