MEdPACTO

Metastasis of pancreatic cancer tumor is successfully inhibited when addressed Vactosertib in combination with PRMT5 protein inhibitor

Confirmed anti-cancer effects in the syngeneic mouse model of pancreatic cancer

 

MedPacto (CEO Seong-jin Kim), a genome-based drug discovery and a clinical-stage biotechnology company, announced that preclinical data of Vactosertib, a TGF-β inhibitor, combination therapy will be highlighted at the 2023·American Association for Cancer Research (AACR) Annual Meeting 2023, which will be held from April 14 - 19, 2023 in Orlando, Florida.

 

The AACR Annual Meeting is the focal point of the cancer research community, where scientists, clinicians, other health care professionals, survivors, patients, and advocates gather to share the latest advances in cancer science and medicine.

 

MedPacto will present preclinical data on the combination therapy of Vactosertib with T1-44, a protein arginine methyltransferase 5 (PRMT5) protein activity inhibitor which was also published in an international journal Cell Death and Disease (IF:8.469).

 

The PRMT5 protein, an enzyme that promotes tumor cell growth, is known to be overexpressed in various cancers including pancreatic ductal adenocarcinoma (PDAC).

 

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 MedPacto representative.