Researchers from the University of California-Irvine's Chao Family Comprehensive Cancer Center found that a genetic pathway in melanoma cells inhibits the cellular mechanism for detecting DNA damage wrought by chemotherapy, thereby building up tolerance to cancer-killing drugs.
Targeting this pathway, comprising the genes RhoJ and Pak1, can be a new approach to treating deadly skin cancer, researchers said.
"If we can find a way to turn off the pathway responsible for this resistance, melanoma tumours would suddenly become sensitive to therapies we've been using for the last 20 years," Dr Anand Ganesan, assistant professor of dermatology and biological chemistry at UCI, said.
The researchers performed a genome-wide scan for genes controlling drug resistance in melanoma cells. Their search identified RhoJ, a gene normally involved in blood vessel growth.
They saw that in response to drug-induced DNA damage in a melanoma cell, RhoJ activated another gene, Pak1, which initiated a molecular cascade suppressing the cell's ability to sense this damage - and blocking the apoptosis process.
"Normally, such drug-induced DNA damage would result in cell death," Ganesan said.
"But this blunting of DNA damage response allows melanoma cells to mutate and proliferate. Being capable of rapid adaptation and change is a hallmark feature of this challenging form of cancer and makes it very difficult to treat," he said in a statement.
The study was published in journal Cancer Research.
