Targeting the KRAS mutation – An old target with new angles!

Juhi Kunde, MA

Dr. Timothy BurnsAfter losing both parents to lung cancer, Dr. Timothy Burns, now an oncologist and researcher specializing in lung cancer at the University of Pittsburgh, committed himself to searching for better treatment options for lung cancer patients.

Because the KRAS mutation is found in 25% of lung cancer patients and there still isn’t a therapy that effectively targets the mutation, Dr. Burns focuses his research on KRAS.

In 2013, LUNGevity funded Dr. Burns’ research to understand why non-small cell lung cancer (NSCLC) patients with a KRAS mutation initially do well when treated with the drug ganetespib but then quickly develop resistance to the treatment.

“I wanted to understand how the drug works,” notes Dr. Burns. “The hope was that by knowing more about how it works, we could overcome the drug resistance and use the treatment more effectively.” 

Researchers know that ganetespib has a good initial effect because it halts the growth cycle of tumor cells. However, this effect doesn’t last long. The tumors usually find a workaround and start growing again. For decades researchers have tried to understand why this drug resistance develops.

By comparing drug-sensitive cells with cells that are drug-resistant, Dr. Burns and his team discovered a change in the amounts of key proteins in the drug-resistant cells. The cells that were resistant to ganetespib had increased levels of several proteins, including CDC25C, which is known to regulate cell growth. This increased protein production is likely to be the cause of drug resistance seen in NSCLC patients who have the KRAS mutation.

Dr. Burns and other researchers are now considering combining ganetespib, or other similar drugs, with treatments that target one or some of these key proteins as a way of overcoming drug resistance in NSCLC patients with the KRAS mutation.

“Our research has provided a way forward with a class of drugs that has been hitting a brick wall for 20 years,” explains Dr. Burns.

Armed with critical information about how KRAS-mutated NSCLC cells are affected by this class of drugs, Dr. Burns is working with pharmaceutical companies that are testing treatments similar to ganetespib. His goal is to give them a deeper understanding of their drugs in order to improve the designs and outcomes of their early-stage clinical trials.

 “I want to help these trials be as smart and successful as possible,” concludes Dr. Burns, “because ultimately it means NSCLC patients can benefit from better treatment options.”

In our next blog, we will discuss some other approaches to targeting KRAS.

Juhi Kunde, MA, is a science writer for LUNGevity. Juhi Kunde

Molecular testing
Non-small cell lung cancer (NSCLC)

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