Dasatinib as a Potential Targeted Therapy for Chronic Pancreatitis: A Narrative Review of Macrophage-PSC Interactions
Main Article Content
Chronic pancreatitis is a long-term inflammatory condition affecting the pancreas, with progression worsening over time. One of the effects of this disease is the formation of scar tissue, which can permanently damage the pancreas and disrupt its functions, both exocrine and endocrine. Chronic pancreatitis can result in various serious complications and even be fatal. In the effort to treat chronic pancreatitis, therapies targeting macrophages have begun to attract attention as an innovative approach. One of the drugs in the spotlight is dasatinib, a tyrosine kinase inhibitor, which has shown the ability to alter the inflammatory response by affecting the macrophage population in the pancreatic microenvironment. This literature review aims to dig deeper into the role of dasatinib in the treatment of chronic pancreatitis and explain the pathophysiology of this disease, especially how macrophage activation contributes to the inflammatory process, as well as the therapeutic effects of dasatinib, we can find new insights to develop more effective treatment strategies.
2. Szatmary P, Grammatikopoulos T, Cai W, Huang W, Mukherjee R, Halloran C, et al. Acute Pancreatitis: Diagnosis and Treatment. Drugs. 2022;82(12):1251–76.
3. Walkowska J, Zielinska N, Karauda P, Tubbs RS, Kurtys K, Olewnik Ł. The Pancreas and Known Factors of Acute Pancreatitis. J Clin Med. 2022;11(19):1–21.
4. Mihoc T, Latcu SC, Secasan CC, Dema V, Cumpanas AA, Selaru M, et al. Pancreatic Morphology, Immunology, and the Pathogenesis of Acute Pancreatitis. Biomedicines. 2024;12(11):1–38.
5. Hart PA, Conwell DL, Krishna SG. Acute and Chronic Pancreatitis. In: Loscalzo J, Fauci A, Kasper D, Hauser S, Longo D, Jameson JL, editors. Harrison’s Principles of Internal Medicine, 21e. New York, NY: McGraw-Hill Education; 2022.
6. Yadav D, Lowenfels AB. The Epidemiology of Pancreatitis and Pancreatic Cancer. Gastroenterology. 2013;144(6):1252–61.
7. Weiss FU, Laemmerhirt F, Lerch MM. Etiology and risk factors of acute and chronic pancreatitis. Visc Med. 2019;35(2):73–81.
8. Ul Hassan MS, Mobusher M, Mansoor MH, Ahmad CA, Ahsan I, Hamza M, et al. Prevalence and Associated Risk Factors of Acute Pancreatitis in Patients With Gallstones: A Cross-Sectional Study. Cureus. 2025;17(5):4–11.
9. Ramsey ML, Conwell DL, Hart PA. Complications of Chronic Pancreatitis. Dig Dis Sci. 2017;62(7):1745–50.
10. Wang Z, Dong S, Zhou W. Pancreatic stellate cells: Key players in pancreatic health and diseases (Review). Mol Med Rep. 2024;30(1):1–18.
11. Abdullah A, Mohd Yunos SNM, Basuno B. A Comprehensive Review of Recent Advances in Scalar Convection-Diffusion Studies. J Adv Res Numer Heat Transf. 2024;27(1):14–27.
12. Park NS, Park YK, Yadav AK, Shin YM, Bishop-Bailey D, Choi JS, et al. Anti-growth and pro-apoptotic effects of dasatinib on human oral cancer cells through multi-targeted mechanisms. J Cell Mol Med. 2021;25(17):8300–11.
13. Abdalla M, Thompson LA, Gurley E, Burke S, Ujjin J, Newsome R, et al. Dasatinib inhibits TGFβ-induced myofibroblast differentiation through Src-SRF Pathway. Eur J Pharmacol. 2015;769:134–42.
14. Manohar M, Verma AK, Venkateshaiah SU, Sanders NL, Mishra A. Pathogenic mechanisms of pancreatitis. World J Gastrointest Pharmacol Ther. 2017;8(1):10.
15. Hashimoto A, Karim MR, Kuramochi M, Izawa T, Kuwamura M, Yamate J. Characterization of Macrophages and Myofibroblasts Appearing in Dibutyltin Dichloride–Induced Rat Pancreatic Fibrosis. Toxicol Pathol. 2020;48(3):509–23.
16. Mayerle J, Sendler M, Hegyi E, Beyer G, Lerch MM, Sahin-Tóth M. Genetics, Cell Biology, and Pathophysiology of Pancreatitis. Gastroenterology. 2019;156(7):1951-1968.e1.
17. Zhang T, Zhang G, Yang W, Chen H, Hu J, Zhao Z, et al. Lnc-PFAR facilitates autophagy and exacerbates pancreatic fibrosis by reducing pre-miR-141 maturation in chronic pancreatitis. Cell Death Dis. 2021;12(11).
18. Chang M, Chen W, Xia R, Peng Y, Niu P, Fan H. Pancreatic Stellate Cells and the Targeted Therapeutic Strategies in Chronic Pancreatitis. Molecules. 2023;28(14).
19. Zeng XP, Wang LJ, Guo HL, He L, Bi YW, Xu ZL, et al. Dasatinib ameliorates chronic pancreatitis induced by caerulein via anti-fibrotic and anti-inflammatory mechanism. Pharmacol Res. 2019;147(May):104357.