The efficacy of the combination treatment of Vactosertib with PRMT5 in pancreatic cancer was published in an international journal Cell Death and Disease (IF: 8.469)
Feb 15, 2023
Combination treatment of PRM5 inhibitor with Vactosertib significantly reduced tumor size and surrounding tissue invasion and significantly improved long-term survival
Combination treatment of PRMT5(protein arginine methyltransferase 5) inhibitor with Vactosertib, an inhibitor of TGF-β signaling, provides support for potential new treatment options for patients with pancreatic cancer which is the most lethal type of cancer and the third leading cause of cancer death with the lowest 5-year survival rate.
On Feb 15th, GILO Research Institute, a foundation where SeongJin Kim, MedPacto CEO, serves as the research director, announced that the combination of T1-44 with the TGF-β signaling inhibitor Vactosertib reduced tumor size and surrounding tissue invasion and significantly improved long-term survival when compared with T1-44 mono treatment, a selective inhibitor of PRMT5 protein activity inhibitor.
The study result was published in the 14th issue of the international journal ‘Cell Death & Disease’ (IF: 8.469).
PRMT5 protein, known as an enzyme that promotes tumor growth, is overexpressed in various cancers including pancreatic ductal adenocarcinoma (PDAC). Recent studies have shown that Protein arginine methyltransferase 5 (PRMT5) is overexpressed in pancreatic cancers and these patients have a worse prognosis. A lot of pharmaceutical companies are developing PRMT5-targeted anti-cancer drugs. The research team investigated the effectiveness of combination treatment of T1-44, an inhibitor of PRMT5 activity, and Vactosertib, a TGF-β signaling inhibitor, was effective on pancreatic tumor growth.
The research team conducted a joint study with Professor Nick B. La Thangue of the University of Oxford, a board-certified authority in tumor biology, to investigate the anti-cancer effect of the combination of T1-44 developed by Professor Nick B. and Vactosertib in the syngeneic mouse model of pancreatic cancer.
The combination treatment group of T1-44 and Vactosertib showed significantly improved results; 60% of mice survived more than 50 days. When compared with T1-44 monotherapy, a selective inhibitor of PRMT5 activity, the combination of T1-44 with the TGF-β1 signaling inhibitor Vactosertib significantly reduced tumor size. The research team concluded that Vactosertib contributed to tumor progression and immune evasion in the tumor microenvironment while increasing the efficacy of combined anti-cancer drugs.
The research team observed changes in the gene expression primarily involved in cancer progression in the combination treatment group of Vactosertib and T1-44. The RNA sequencing analysis revealed that the combination of T1-44 and Vactosertib significantly altered the expression of genes such as cell migration, extracellular matrix, and apoptotic processes. In particular, the expression of BTG2 which is known as a tumor suppressor factor in various cancers was significantly increased when addressed with combination treatment.
“The combination therapy of Vactosertib and T1-44 is synergistic for pancreatic cancer significantly increasing the expression level of BTG2, tumor suppressor gene which improves survival rate in the syngeneic mouse model of pancreatic cancer by suppressing metastasis and reducing the size of the tumor”, “We expect this novel combination therapy suggests the new treatment option for the patients with pancreatic cancer,” stated SeongJin Kim, research director of GILO and the CEO of MedPacto.