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Pancreatic cancer: Researchers find drug that reverses resistance to chemotherapy

Submitted by on 25 December, 2020 – 4:32 pm
For the first time, researchers have shown to inhibit the action of an enzyme called TAK-1, may make pancreatic cancer cells sensitive to chemotherapy, opening the way for the development of a new drug to treat the disease.

Dr. Davide Melisia told Congress on Europe’s largest cancer, ECCO 15 – ESMO 34, in Berlin today (Thursday 24 September) that resistance to chemotherapy is the biggest challenge in treating pancreatic cancer.

“Pancreatic cancer is an incurable malignancy resistant to all cancer treatment. Orientation TAK-1 could be a strategy to reverse this resistance, increasing the effectiveness of chemotherapy,” said Dr. Melisia, which until early September was a Fellow at the MD Anderson Center in Houston (Texas, USA), which has now passed to a personal position of the National Cancer Institute in Naples (Italy). “In recent years we have studied the role of a cytokine or regulatory protein called transforming growth factor beta (TGFbeta) in the development of pancreatic cancer. Recently we have focused our attention on a unique enzyme activated by TGFbeta, TAK-1, as a mediator for this extreme drug resistance “.

Dr. Melisia and colleagues investigated the expression of TAK-1 (TGFbeta-activated kinase-1) in pancreatic cell lines and developed a drug that could inhibit TAK-1. They tested the activity of TAK-1 inhibitor alone and in combination with anticancer drugs gemcitabine, oxaliplatin and SN-38 (a metabolite of the anti-cancer drug irinotecan) in cell lines, and the -1 inhibitor TAK activity in combination with gemcitabine against pancreatic cancer in mice.

“The use of this inhibitor TAK-1 increased the sensitivity of pancreatic cells to three chemotherapy drugs. By combining the classic with anti-cancer drugs, which were able to use doses of medication to 70 times lower compared with the control kill as many cancer cells. In mice, we were able to significantly reduce tumor bulk, to prolong survival of mice, and to reduce toxicity by combining inhibitors TAK-1 with very low doses of classical chemotherapy drug, gemcitabine, which would have otherwise been ineffective, “said Dr. Melisia.

The use of gemcitabine in her own cancer in mice was ineffective due to drug-resistant nature of the disease. However, once combined with the inhibitor TAK-1, Dr. Melisia and his colleagues saw a 78% reduction in tumor volumes. “The average median survival for control, TAK-1 inhibitor, gemcitabine in your account, or TAK-1 inhibitor in combination with gemcitabine was 68, 87, 82 and 122 days respectively,” he said.

“This is the first time that TAK-1 has been identified as an important target for the treatment of solid tumors and is a valid approach to reverse the intrinsic drug resistance of pancreatic cancer. The TAK-1 inhibitor used in this study is an interesting drug that deserves further development for treating pancreatic cancer. In the near future, we will consider whether it is also capable of other chemotherapeutic agents such as oxaliplatin, 5-FU or irinotecan, work pancreatic cancer in mice.

“Our main goal is to make this combined approach the bench to bedside, conducting a clinical trial could demonstrate the safety of this inhibitor TAK-1 in combination with gemcitabine, and its effectiveness in patients with pancreatic cancer.

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