Until recently I didn't realize that Inflammatory Bowel Disease was a risk-factor for CRC. So I thought I'd go down the rabbit hole and look into it a bit. Came across some new information on "NETs" and how metastasis plays out in the body, and favors the liver in mCRC. Worth sharing:
"IBD significantly promotes neutrophil infiltration into the gut, creating a chronic inflammatory environment that is a major driver for the development and progression of Colorectal Cancer. Crohn's and ulcerative colitis cause persistent gut inflammation, attracting massive numbers of neutrophils to the intestinal lining. Here they produce matrix metalloproteinases and VEGF, which promote tumor invasion and angiogenesis. They also release Reactive Oxygen Species, inflammatory cytokines like IL-1b, IL-6, and TNF-a, and form Neutrophil Extracellular Traps (NETs)..."
Turns out NETs are "web-like structures of DNA and cytotoxic proteins" that are released by agitated neutrophils. "These NETS can capture circulating tumor cells and promote their migration and metastasis to distant organs, especially in the liver. The release of CCL5 can amplify NETosis in specific neutrophil subsets." And of course leronlimab will control CCL5 and smack down NETosis. I wonder if we are going to hear more about NETs in the biomarker presentation you mention, or in the CRC/liver metastasis study at City of Hope.
When I heard the news about leronlimab and ICIs in TNBC, way back when,
my first thought was--why not just scrap mCRC and get straight into a breast cancer trial? But above and beyond the time that might have been lost in that kind of bureaucratic re-shuffle, it's clear to me that Cytodyn made the right call on pursuing the mCRC indication. There are a ton of papers specifically on the CCL5-CCR5 Axis in colorectal cancer, and I suspect they read them all. And figured out that mCRC--with the NETs and mets connection, the liver issues, and inflammatory co-morbidities--would be a cancer very, and perhaps even uniquely, vulnerable to CCR5 blockade. And it sure appears they got it right.
I think you hit the nail on the head--"They're such good results that they're already working on presentations about both biomarkers and outcomes. That's fantastic." Already talking about positive outcomes, this early in the trial? Yowza!
Looks like open waters ahead... but watch out! We are gonna make some waves...
"IBD significantly promotes neutrophil infiltration into the gut, creating a chronic inflammatory environment that is a major driver for the development and progression of Colorectal Cancer. Crohn's and ulcerative colitis cause persistent gut inflammation, attracting massive numbers of neutrophils to the intestinal lining. Here they produce matrix metalloproteinases and VEGF, which promote tumor invasion and angiogenesis. They also release Reactive Oxygen Species, inflammatory cytokines like IL-1b, IL-6, and TNF-a, and form Neutrophil Extracellular Traps (NETs)..."
Turns out NETs are "web-like structures of DNA and cytotoxic proteins" that are released by agitated neutrophils. "These NETS can capture circulating tumor cells and promote their migration and metastasis to distant organs, especially in the liver. The release of CCL5 can amplify NETosis in specific neutrophil subsets." And of course leronlimab will control CCL5 and smack down NETosis. I wonder if we are going to hear more about NETs in the biomarker presentation you mention, or in the CRC/liver metastasis study at City of Hope.
When I heard the news about leronlimab and ICIs in TNBC, way back when,
my first thought was--why not just scrap mCRC and get straight into a breast cancer trial? But above and beyond the time that might have been lost in that kind of bureaucratic re-shuffle, it's clear to me that Cytodyn made the right call on pursuing the mCRC indication. There are a ton of papers specifically on the CCL5-CCR5 Axis in colorectal cancer, and I suspect they read them all. And figured out that mCRC--with the NETs and mets connection, the liver issues, and inflammatory co-morbidities--would be a cancer very, and perhaps even uniquely, vulnerable to CCR5 blockade. And it sure appears they got it right.
I think you hit the nail on the head--"They're such good results that they're already working on presentations about both biomarkers and outcomes. That's fantastic." Already talking about positive outcomes, this early in the trial? Yowza!
Looks like open waters ahead... but watch out! We are gonna make some waves...
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