DRUG STOPPING CANCER GROWTH MAY BE GOOD VS COVID: STUDY

Cancer doctors may soon have a new tool for treating melanoma and other types of cancer, thanks to work being done by researchers at the University of Colorado Cancer Center. They may even find it good in combatting COVID-19, Science Daily reported.

In a paper published in the journal Proceedings of the National Academy of Sciences (PNAS) last month, CU Cancer Center members Dr. Mayumi Fujita, Dr. Angelo D'Alessandro, Dr. Morkos Henen, Dr. Beat Vogeli, Dr. Eric Pietras, Dr. James DeGregori, Dr. Carlo Marchetti and Dr. Charles Dinarello, along with Isak Tengesdal, a graduate student in the Division of Infectious Diseases at the University of Colorado School of Medicine, detail their work on NLRP3, an intracellular complex that has been found to participate in melanoma-mediated inflammation, leading to tumor growth and progression.

By inhibiting NLRP3, the researchers found, they can reduce inflammation and the resultant tumor expansion.

Specifically, NLRP3 promotes inflammation by inducing the maturation and release of interleukin-1-beta, a cytokine that causes inflammation as part of the normal immune response to infection. In cancer, however, inflammation can cause tumors to grow and spread. "NLRP3 is a member of a larger family that is involved in sensing danger signals," Marchetti says.

"It is a receptor that surveils the intercellular compartment of a cell, looking for dangerous molecules or pathogens. When NLRP3 recognizes these signals, it leads to the activation of caspase-1, a protein involved in the processing and maturation of interleukin-1-beta into its biological active form, causing an intense inflammatory response. We found that in melanoma, this process is dysregulated, resulting in tumor growth."

The oral NLRP3 inhibitor used in their study (Dapansutrile) has already been shown to be effective in clinical trials to treat gout and heart disease, and it is currently being tested in COVID-19 as well. The CU cancer researchers are now trying to find out if this NLRP3 inhibitor can be successfully used in melanoma patients who are resistant to checkpoint inhibitors.

"Checkpoint inhibitors increase the efficacy of the immune system to kill tumors, but sometimes tumors become resistant to this treatment," Marchetti says. "A big part of cancer research now is to find therapies that can be combined with checkpoint inhibitors to improve their efficacy."

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