On December 3, 2021 Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company focused on developing novel drug candidates for immuno-inflammatory diseases, reported the publication of preclinical research of zunsemetinib in pancreatic cancer in the peer-reviewed journal Science Translational Medicine, on December 1, 2021 (Press release, Aclaris Therapeutics, DEC 3, 2021, View Source [SID1234596443]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The article, entitled "The MK2/Hsp27 axis is a major survival mechanism for pancreatic ductal adenocarcinoma under genotoxic stress," presents the results from a preclinical study using patient-derived cell lines and an autochthonous pancreatic ductal adenocarcinoma mouse model that evaluated the role of MK2, as well as the impact of zunsemetinib (ATI-450), Aclaris’ investigational oral MK2 inhibitor, in pancreatic cancer. This study was a multi-year collaboration between Aclaris and Washington University School of Medicine, led by the laboratory of Dr. Kian-Huat Lim, MD, PhD, Associate Professor in Oncology and Dr. Patrick Grierson, MD, PhD, Assistant Professor in Oncology.
In the study, Dr. Lim and his team identified the MK2/HSP27 axis as an important resistance mechanism resulting in pancreatic tumor cell survival following exposure to components of FOLFIRINOX chemotherapy – the current standard-of-care treatment for pancreatic cancer. His team also demonstrated that DNA damage induced by FOLFIRINOX chemotherapy components upregulated tumor necrosis factor alpha (TNFa) in pancreatic cancer cells, which had the dual effect of impacting cell death and cell survival, and that the selective inhibition of MK2 downstream of TNFa signaling abrogated survival through blocking HSP27 activation and beclin1 mediated autophagy, which allowed TNFa to execute its pro-death mechanism. With this understanding, his team then showed that mouse survival in an autochthonous KPPC model of pancreatic cancer was statistically significantly (p<0.001) extended when dosed with zunsemetinib in combination with FIRINOX (a murine version of FOLFIRINOX).
"This study introduces a new MK2-targeted approach for the treatment of pancreatic cancer," said Dr. Lim. "We are very excited about the potential of this therapeutic combination and believe it should be advanced into clinical trials to determine whether MK2 inhibition can strengthen the effect of mainstay FOLFIRINOX chemotherapy in patients with pancreatic cancer without incurring additional side effects."
Based on these results and clinical data generated from Aclaris’ clinical development program with zunsemetinib, Aclaris is considering a future clinical program for the treatment of patients with pancreatic cancer using one of Aclaris’ other MK2 inhibitor drug candidates.
The authors of the article are Patrick M. Grierson, Paarth B. Dodhiawala, Yi Cheng, Timothy Hung-Po Chen, Iftikhar Ali Khawar, Qing Wei, Daoxiang Zhang, Lin Li, John Herndon, Joseph B. Monahan, Marianna B. Ruzinova, and Kian-Huat Lim, and the article can be accessed here: View Source