Foundation fund

Study the role of different signaling pathways

University of Colorado (CU) Cancer Center member Tejas PatilMD, is one of the three researchers receive a combined grant of $1 million from the Hamoui Foundation and the LUNGevity Foundation to study RET-positives lung cancer.

RET is a motor mutation found in about 1-2% of people with non-small cell lung cancer. Patients diagnosed with RET-positive lung cancer generally receive therapies that target the RET mutation, but a portion of these patients develop resistance to targeted therapies. Patil’s research examines how this resistance occurs and how two other pathways, known as the EGFR and MET signaling pathways, play a role.

“What happens is that cancer cells develop escape mechanisms to survive in this environment,” says Patil, assistant professor of medical oncology at University of Colorado School of Medicine. “It’s kind of an evolutionary arms race where, to adapt to this new environment, cancer cells start looking to exploit other pathways to survive.”

Target resistance

Patil will lead a multi-site study to assess the role of the drug amivantamab – a bispecific antibody that specifically targets both EGFR and MET – in patients with RET-positive lung cancer whose cancer develops resistance to targeted therapy. Amivantamab is already FDA-approved to treat another type of lung cancer mutation, and Patil hopes it will be effective in RET as well.

“What’s interesting about this drug is that it blocks both EGFR and MET, which are the very pathways we want to study in this population as potential ways in which cancer evades effects of RET targeted therapy,” he says. “If we combine RET treatment with this antibody, will it actually affect the results? This is what we are trying to answer with this clinical trial.

The five-year trial, which is due to open this year, will measure patients at three different time points: before they start treatment, after they have developed resistance to the targeted therapy and after they have been treated with amivantamab.

“If they develop resistance to their first-line targeted therapy, if there’s a signal to suggest that EGFR or MET seem to be involved, then this combination makes sense,” says Patil. “If something else seems to be happening – if they have a different pathway or have a different mutation – then maybe it’s not the optimal treatment. It’s about really dissecting how these patients develop resistance. , and then very appropriately select patients for the right combination.

Beyond the RET

Receiving the funds from the Hamoui Foundation and the LUNGevity Foundation was very meaningful, says Patil, not only for research into RET-positive lung cancer, but because researchers believe that other cancers also use EGFR pathways and MET as a means of resistance. This is another question his research aims to answer.

“If what we suspect is true, that cancers use these EGFR and MET pathways to develop resistance, this has implications for how we think about resistance for patients outside of RET,” he says. “It’s exciting for LUNGevity to fund this because I think it has a broad reach.”

If the research confirms his hypothesis, Patil says, the study will be a game-changer in how doctors treat patients with RET-positive lung cancer who develop resistance to targeted therapy.

“It offers patients the option of having another line of therapy, should they progress on their initial targeted therapy,” he says. “For RET-positive patients, as they progress on their targeted therapy, which is first-line treatment, there really aren’t a lot of options outside of chemotherapy. This potentially offers a chemotherapy-free alternative, should this be a viable trial.

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