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MPN Workshop of the Carolinas 2025 | Targeting NET formation in patients with CMML: a novel therapeutic approach
In this video, Ami Patel, MD, Huntsman Cancer Institute, Salt Lake City, UT, comments on the potential of targeting neutrophil extracellular trap (NET) formation in chronic myelomonocytic leukemia (CMML) as a novel therapeutic strategy. Dr Patel highlights that NET formation contributes to chronic inflammation, immunosuppression, and cancer progression, and that a novel compound, neonatal NET inhibitory factor, has been identified to inhibit NET formation. Dr Patel suggests that NET inhibitors may be most effective when used in conjunction with standard cytoreductive therapies, rather than as single agents, to target multiple disease pathways. This interview took place at the 2nd Annual MPN Workshop of the Carolinas, held in Charlotte, NC.
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Transcript
So, across many different disease types ranging from autoimmune disease to solid cancers, there’s increased inflammation. And it’s been found that neutrophil extracellular trap formation or NET formation in these inflammatory diseases contributes to the chronic inflammation and also drives immunosuppression via T-cell exhaustion, contributing to cancer metastasis, cancer spread, cancer cell proliferation, and immune evasion mechanisms...
So, across many different disease types ranging from autoimmune disease to solid cancers, there’s increased inflammation. And it’s been found that neutrophil extracellular trap formation or NET formation in these inflammatory diseases contributes to the chronic inflammation and also drives immunosuppression via T-cell exhaustion, contributing to cancer metastasis, cancer spread, cancer cell proliferation, and immune evasion mechanisms.
So I have a laboratory that is dedicated to studying CMML and developing new therapies for CMML, and one of the things that we’re looking at right now is dysregulated neutrophil extracellular trap formation in CMML. And so my lab has found that NETs are abnormally increased in CMML. And we have collaborators at the University of Utah who have identified a compound, a novel compound actually, that was first discovered in cord blood that actually inhibits NET formation. It’s called neonatal NET inhibitory factor. And so we’re interested in using this compound pre-clinically to see if it inhibits NETosis in CMML.
So I think that NET inhibitors on their own are unlikely to be used as single agents ultimately, because they are…we can think of them as anti-inflammatory agents. I think they would be used most in conjunction with more standard cytoreductive therapies like hypomethylating agents or perhaps small molecule inhibitors. So I think that their use as a single agent is somewhat limited, but in conjunction with other agents targeting other disease pathways, it could be quite effective.
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Disclosures
Genentech, Menarini-Stemline, Novartis.
