New drug can reduce inflammation, tumour expansion

A team of scientists at the University of Colorado Cancer Center claim to have found a drug that can reduce inflammation and the resultant tumour expansion.

The potential treatment can help cancer doctors as they may soon have a new tool for treating melanoma and other types of cancer.

In a paper published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS), scientists from the University of Colorado Anschutz Medical Campus detailed their work on NLRP3, an intracellular complex that has been found to participate in melanoma-mediated inflammation, leading to tumour growth and progression. By inhibiting NLRP3, the researchers found, they can reduce inflammation and the resultant tumour 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 tumours to grow and spread.

"NLRP3 is a member of a larger family that is involved in sensing danger signals," Carlo Marchetti, PhD, said. "It is a receptor that surveils the intercellular compartment of a cell, looking for dangerous molecules or pathogens. When NLRP3 recognises these signals, it leads to the activation of caspase-1, a protein involved in the processing and maturation of interleukin-1-beta into its biologically active form, causing an intense inflammatory response. We found that in melanoma, this process is dysregulated, resulting in tumour growth."

The oral NLRP3 inhibitor used in their study (Dapansutrile) has already 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 tumours, but sometimes tumours become resistant to this treatment," Marchetti said. "A big part of cancer research now is to find therapies that can be combined with checkpoint inhibitors to improve their efficacy."

With the hypothesis that an NLRP3 inhibitor is one of those therapies, CU Cancer Center researchers are studying the drug's effects on melanoma, as well as breast cancer and pancreatic cancer. In addition to improving the immune response, the NLRP3 inhibitor can also help reduce the side effects of checkpoint inhibitors. Marchetti said this research can make a big difference for melanoma patients who do not respond to checkpoint inhibitors alone.

"This was a very collaborative project that involved a lot of members of the university, and we are very excited about it," he said. This project is important because it further shows that NLRP3-mediated inflammation plays a critical role in the progression of melanoma, and it opens new strategies to improve patient care.

( With inputs from ANI )