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Response to PLX4032 drug short lived in BRAF-mutated metastatic melanoma patients

August 31, 2015

"It's important to find all the mechanisms of acquired drug resistance in this type of melanoma and figure out how to target them using drugs designed to hit those specific mechanisms," he said. "We've found two mechanisms in two subsets of melanoma and we'll need different drugs to treat those two subsets."

Going forward, Lo and his team will study the resistance mechanisms of the two subsets discovered and any others uncovered later to perhaps find better targets for therapy. For example, targeting the cell surface protein overexpression may prove more difficult than finding what causes the overexpression further upstream and homing in on that.

"How does the cell surface receptor get turned on in the first place?" Lo said. "We need to trace it back to its origin, find out what machinery is turning it on and shut that down."

Lo's study is an example of the translational research focus at the Jonsson Cancer Center. The tissues from the patients in the clinic were studied in the lab, where Lo and his team found what was causing resistance in some cases. That information will be used to find drugs to target those mechanisms that will then be brought back into the clinic to be tested in clinical trials.

"Working with the patients and then working in the lab gives me a different perspective," Lo said. "When patients ask what will happen to them if the experimental drug stops working, we can tell them that we're working 24/7 in our laboratory to figure out why that happens and discover a way to stop it."

About 68,000 cases of melanoma will be diagnosed in Americans this year alone. Of those, more than 8,700 people will die. For patients with metastatic melanoma, like those in the Jonsson Cancer Center study, there are few effective treatments, so it's vital to come up with alternative therapies, Lo said.

Source: University of California - Los Angeles