#Aspirin Use and Reduced Risk of #Pancreatic Cancer

http://cebp.aacrjournals.org/content/early/2016/12/16/1055-9965.EPI-16-0508

Regular use of aspirin thus appears to reduce risk of pancreatic cancer by almost half.

Impact: People who take aspirin for prevention of other diseases likely also reduce their risk of pancreatic cancer. Aside from benefits for both cardiovascular disease and certain cancers, long-term aspirin use entails some risks of bleeding complications, which necessitates risk–benefit analysis for individual decisions about use

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Suppression of stromal-derived Dickkopf-3 (DKK3) inhibits tumor progression and prolongs survival in #pancreatic ductal #adenocarcinoma

http://stm.sciencemag.org/content/10/464/eaat3487

Killing tumors by targeting their neighbors

Pancreatic cancer is infamous for its bad prognosis, as well as for its dense stroma. Most therapies target the tumor cells themselves rather than the stroma, but now, Zhou et al. identified a therapeutic target called DKK3, which is produced by pancreatic stellate cells. The authors showed that this protein was present in most of the human pancreatic tumors in their study sample. They also demonstrated the effectiveness of ablating DKK3, either by genetic means or with a monoclonal antibody. The antibody treatment reduced tumor growth and extended survival in mouse models, especially when combined with an immune checkpoint inhibitor, demonstrating its therapeutic potential.

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Treatment with #incretins does not increase the risk of #pancreatic diseases compared to older anti‐hyperglycaemic drugs, when added to metformin: real world evidence in people with Type 2 diabetes

https://onlinelibrary.wiley.com/doi/10.1111/dme.13835

In the DPP‐4i group, the adjusted mean time to acute pancreatitis was 2.63 95% confidence intervals (CI) 2.38, 2.88 years; time to pancreatic cancer was 2.70 (2.19, 3.21) years; and time to other diseases of the pancreas was 2.73 (2.33, 3.12) years. Compared with DPP‐4i, the insulin group developed acute pancreatitis 0.48 years (P < 0.01) earlier and the GLP‐1RA group developed pancreatic cancer 3 years later (P < 0.01). However, with the constraint of no event within 6 months of insulin initiation, the risk of acute pancreatitis in the insulin group was insignificant. No other significant differences were observed between groups.

Conclusions
No significant differences in the risk of developing pancreatic diseases in those treated with various anti‐hyperglycaemic drug classes were found.

NAD+ depletion by type I interferon signaling sensitizes #pancreatic cancer cells to NAMPT inhibition
https://2medical.news/2021/02/20/nad-depletion-by-type-i-interferon-signaling-sensitizes-pancreatic-cancer-cells-to-nampt-inhibition/

Emerging evidence suggests that intratumoral interferon (IFN) signaling can trigger targetable vulnerabilities. A hallmark of pancreatic ductal adenocarcinoma (PDAC) is its extensively reprogrammed metabolic network, in which nicotinamide adenine dinucleotide (NAD) and its reduced form, NADH, are critical cofactors. Here, we show that IFN signaling, present in a subset of PDAC tumors, substantially lowers NAD(H) levels through up-regulating the expression of NAD-consuming enzymes PARP9, PARP10, …

NOX4 links metabolic regulation in #pancreatic #cancer to endoplasmic reticulum redox vulnerability and dependence on PRDX4

https://2medical.news/2021/05/08/nox4-links-metabolic-regulation-in-pancreatic-cancer-to-endoplasmic-reticulum-redox-vulnerability-and-dependence-on-prdx4/

Changes in #metabolic syndrome status are associated with altered risk of #pancreatic cancer: A nationwide cohort study

https://2medical.news/2021/10/19/changes-in-metabolic-syndrome-status-are-associated-with-altered-risk-of-pancreatic-cancer-a-nationwide-cohort-study/