Updated: April 22, 2021, 10:22 a.m. IS
Nagoya, Japan, April 22nd (ANI): Researchers have discovered a molecular pathway that increases chemotherapy resistance in some pancreatic cancer patients. Targeting an RNA to disrupt its activity could improve the patient’s response to therapy and increase overall survival.
The study, led by researchers and colleagues at Nagoya University in Japan, was published in the journal Cancer Research.
“Pancreatic cancer is one of the most aggressive human malignancies with a median medical survival of less than five months,” says cancer biologist Yutaka Kondo of Nagoya University’s Graduate School of Medicine. “This poor prognosis is partly due to the lack of effective therapeutic strategies for pancreatic cancer. Therefore, more effective treatments are urgently needed.”
Kondo and his colleagues focused on a long non-coding RNA (lncRNA) called taurine upregulation gene 1 (TUG1). lncRNAs are gene regulators, some of which have recently been identified to help some cancers resist chemotherapy. TUG1 is already known to be overexpressed in gastrointestinal cancers that have a poor prognosis and are resistant to chemotherapy.
The researchers found that TUG1 was overexpressed in a group of patients with ductal pancreatic adenocarcinoma. These patients were resistant to standard 5-fluorouracil (5-FU) chemotherapy and died much earlier than cancer patients with low TUG1 expression levels.
Further laboratory tests showed that TUG1 counteracts a specific microRNA, resulting in increased activity of an enzyme called dihydropyrimidine dehydrogenase, which breaks down 5-FU into a compound that cannot kill cancer cells.
Kondo and his team found that they can suppress TUG1 during 5-FU treatment of mice with pancreatic cancer by using antisense oligonucleotides attached to a specially designed, cancer-targeted drug delivery system. Antisense oligonucleotides disrupt gene expression.
“Our data provide evidence that our therapeutic approach to pancreatic cancer could show promise,” says Kondo.
The team is now planning further laboratory tests to test the effectiveness of their therapy strategy. (ANI)