Oncologists may soon find another option in treating melanoma or other cancer types. A research team from the University of Colorado Cancer Center released study findings in the journal PNAS last month. They detailed their studies on NLRP3, an intracellular complex found to participate in melanoma-mediated inflammation that leads to tumor growth and progression.
Inhibiting NLRP3 Can Help Stop Growth of Cancer Tumors
By inhibiting NLRP3, the researchers discovered that they could reduce inflammation and the consequent tumor expansion.
NLRP3 fosters inflammation by causing the maturation and release of interleukin-1-beta, a cytokine that instigates inflammation due to the normal immune response to infection. In cancer, though, this inflammation would allow tumors to develop and flourish.
NLRP3, researchers said, is part of a family that senses danger signals.
"It is a receptor that surveils the intercellular compartment of a cell, looking for danger 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," said Carlo Marchetti, Ph.D. of the CU Cancer Center and among the authors of the study.
Wonder Inhibitor Tested for Cancer Treatments
The oral inhibitor of NLRP3 utilized in the study-Dapansutrile-proved to be effective in clinical trials to treat heart disease and gout, and, if further tests would be successful, it could also treat COVID-19. The researchers from the CU Cancer Center are now attempting to find out if this NLRP3 inhibitor can be used in melanoma sufferers, who show resistance to checkpoint inhibitors.
Such checkpoint inhibitors boost the efficacy of the immune system to overcome and waylay tumors, but there are times tumors become resistant to this therapy. Present cancer research delves on finding new treatments that can be mixed with checkpoint inhibitors to strengthen its efficacy, researchers noted.
Current Studies on NLRP3 for Melanoma, Breast and Pancreatic Cancer
As the NLRP3 inhibitor is being considered as a possible treatment, researchers are looking into the drug's effects on melanoma, breast cancer, and pancreatic cancer. Apart from enhancing the immune response, the NLRP3 inhibitor can also help decrease side effects of checkpoint inhibitors. This research can really offer hope for melanoma patients who show resistance to checkpoint inhibitors.
This initiative is significant because it shows that the NLRP3-mediated inflammation plays a crucial role in the development of melanoma, and that it leads to creating new strategies to enhance patient care.
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