Ecco logoIt is claimed that for the first time, researchers have illustrated that by apparently restraining the action of an enzyme known as TAK – 1, it may be likely to make pancreatic cancer cells sensitive to chemotherapy, thus creating an opportunity for the development of a new drug to treat the disease.

It was mentioned by Dr Davide Melisi that the resistance to chemotherapy was supposedly the biggest challenge to treat pancreatic cancer.

Dr Melisi, who until the start of September was a Fellow at the M.D. Anderson Center in Houston (Texas, USA); he has now moved to a staff position at the National Cancer Institute in Naples (Italy), commented, “Pancreatic cancer is an incurable malignancy, resistant to every anti-cancer treatment. Targeting TAK-1 could be a strategy to revert this resistance, increasing the efficacy of chemotherapy. During the past few years we have been studying the role played by a cytokine or regulatory protein called Transforming Growth Factor beta (TGFbeta) in the development of pancreatic cancer. Recently we focused our attention on a unique enzyme activated by TGFbeta, TAK-1, as a mediator for this extreme drug resistance.”

The expression of TAK-1 was apparently examined by Dr Melisi and his colleagues in pancreatic cell lines and apparently formed a drug that was supposedly able to slow down TAK-1. They claimed to test the activity of the TAK-1 inhibitor on its own and in alliance with the anti-cancer drugs gemcitabine, oxaliplatin and SN-38 which is claimed to be a metabolite of the anti-cancer drug irinotecan in cell lines, and the movement of the TAK-1 inhibitor apparently joined with gemcitabine against pancreatic cancer in mice.

Dr Melisi, mentioned, “The use of this TAK-1 inhibitor increased the sensitivity of pancreatic cells to all three chemotherapeutic drugs. By combining it with classic anti-cancer drugs, we were able to use doses of drugs up to 70 times lower in comparison with the control to kill the same number of cancer cells. In mice, we were able to reduce significantly the tumour volume, to prolong the mice survival, and to reduce the toxicity by combining the TAK-1 inhibitor with very low doses of a classic chemotherapeutic drug, gemcitabine, that would have been ineffective otherwise.”

The use of gemcitabine on its own against the cancer in mice was believed to be unsuccessful because of the drug resistant nature of the disease. Nevertheless, once it was joined with the TAK-1 inhibitor, an approximate 78% drop in tumor volumes was observed by Dr. Melisi and colleagues.

Dr. Melisi remarked, “The median average survival for the control, TAK-1 inhibitor, gemcitabine on its own, or TAK-1 inhibitor combined with gemcitabine was 68, 87, 82 and 122 days respectively.”

Dr. Melisi further quoted, “This is the first time that TAK-1 has been indicated as a relevant target for the treatment of a solid tumour and that it is a valid approach to reverting the intrinsic drug resistance of pancreatic cancer. The TAK-1 inhibitor used in this study is an exciting drug that warrants further development for the treatment of pancreatic cancer. In the near future, we will study whether it is also able to make other chemotherapeutic agents, such as oxaliplatin, 5-FU or irinotecan, work against pancreatic cancer in mice.”

Dr. Melisi mentioned that their main goal is to translate this combination approach from the bench to the bedside, conducting a clinical trial that could demonstrate the safety of this TAK-1 inhibitor in combination with gemcitabine, and its efficacy, in pancreatic cancer patients.

This was put forth by Melisi in Europe’s Cancer Congress, ECCO 15 – ESMO, Berlin.