Researchers have identified more than 30 breast cancer gene targets-including several novel genes-that are involved in drug resistance to a leading chemotherapy treatment.
The study conducted by Josh LaBaer`s research team in the Biodesign Institute at Arizona State University may one-day empower physicians with a more personalized approach to therapy as well as a new tool for the early screening of those that may ultimately become resistant to chemotherapy.
Drugs like tamoxifen have been part of the standard treatment regimen for many breast cancer patients and saved countless lives. Unfortunately, a very serious therapeutic problem can occur when the drug loses its potency over time as women develop a resistance to the drug treatment, and tumours reemerge.
Using a well-established cell model for breast cancer along with the LaBaer lab`s extensive collection of fully sequenced human genes, the team performed the largest genetic screen of its kind-testing the ability of 500 regulatory proteins, called kinases, that have been implicated in tumour growth and drug resistance.
"Kinases turn out to be a key drug target and we wanted to take advantage of the large number of kinase genes available in the lab," said Laura Gonzalez, lead author of the study.
By comparing gene expression patterns in cells that were sensitive or resistant in response to tamoxifen, the group identified a suite of genes that failed to respond to the drug.
Encouragingly, these genes were found only in the resistant cells.
Furthermore, the team correlated their cell studies back to the clinic, finding a drug resistance signature that predicted the early relapse of breast cancer for women taking tamoxifen in two different clinical cohorts.
The team identified more than 30 kinases that repeatedly allowed the sensitive cells to grow in the presence of drug. Several were already known, but many were novel.
The findings were published in the journal Proceedings of the National Academy of Sciences.