As personalized medicine comes to the fore, clinics have started tailoring cancer treatment based on the unique cancer mutations that an individual harbors. In a new study, researchers have combined mutated genes and drugs in a large screening for better cancer medicine, unearthing 172 new effective combinations.
Senior author Trey Ideker and his group at UC San Diego School of Medicine published their results in the journal Molecular Cell.
Their approach in identifying new cancer drugs was sought out in a two-hit strategy. They looked for genetic interactions between tumor-suppressor genes and their co-regulated genes. In doing so, they could choose to hit both with a drug--increasing the effectiveness in killing the cancer cells.
They first took yeast versions of human tumor-suppressor genes and “druggable” gene targets. This allowed them to screen 169,000 interactions in a cost-effective way, harnessing genetics to delete genes in combinations, to find the best combinations of drugs that could kill mutated yeast cells.
From this they brought forward 21 drugs that were most effective in killing yeast cells. They then screened these in human cancer cells with 112 different tumor-suppressor gene mutations. They found 172 drug-gene mutation combinations that killed both yeast cells and human cancer cells.
The promise for this type of work lies in better informing oncologists about the combinations of drug-gene interactions, helping them to plan a more effective drug regimen.
"We've created an important translational research resource for other scientists and oncologists," said co-first author Dr. John Paul Shen in a university news release. "And since many of the cancer-killing interactions we discovered involve already FDA-approved drugs, it may mean they could reach clinical translation rapidly. If these results are validated in subsequent testing, in the future an oncologist will have many more options for precision cancer therapy."