Inhibiting the action of an enzyme called TAK-1 reverses pancreatic cancer resistance to chemotherapy
, a finding that could lead to the development of a new way to treat the disease, researchers say.
Pancreatic cancer is resistant to every currently available anti-cancer treatment.
"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" in pancreatic cancer, study author Dr. Davide Melisi said in a news release from the European Cancer Organization.
He and his colleagues developed a TAK-1 inhibitor and tested it on its own and in combination with the anti-cancer drugs gemcitabine, oxaliplatin and SN-38 (a metabolite of the anti-cancer drug irinotecan) in pancreatic cancer cell lines. They also tested the TAK-1 inhibitor combined with gemcitabine against pancreatic cancer
in mice.
"The use of this TAK-1 inhibitor increased the sensitivity of pancreatic cells to all three chemotherapeutic drugs," Melisi said.
"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 tumor 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," Melisi added.
The study was scheduled for presentation Sept. 24 at the joint meeting of the European Cancer Organization and the European Society for Medical Oncology in Berlin.
"This is the first time that TAK-1 has been indicated as a relevant target for the treatment of a solid tumor and that it is a valid approach to reverting the intrinsic drug resistance of pancreatic cancer," Melisi stated. "The TAK-1 inhibitor used in this study is an exciting drug that warrants further development for the treatment of pancreatic cancer."
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, a finding that could lead to the development of a new way to treat the disease, researchers say.
Pancreatic cancer is resistant to every currently available anti-cancer treatment.
"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" in pancreatic cancer, study author Dr. Davide Melisi said in a news release from the European Cancer Organization.
He and his colleagues developed a TAK-1 inhibitor and tested it on its own and in combination with the anti-cancer drugs gemcitabine, oxaliplatin and SN-38 (a metabolite of the anti-cancer drug irinotecan) in pancreatic cancer cell lines. They also tested the TAK-1 inhibitor combined with gemcitabine against pancreatic cancer
in mice.
"The use of this TAK-1 inhibitor increased the sensitivity of pancreatic cells to all three chemotherapeutic drugs," Melisi said.
"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 tumor 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," Melisi added.
The study was scheduled for presentation Sept. 24 at the joint meeting of the European Cancer Organization and the European Society for Medical Oncology in Berlin.
"This is the first time that TAK-1 has been indicated as a relevant target for the treatment of a solid tumor and that it is a valid approach to reverting the intrinsic drug resistance of pancreatic cancer," Melisi stated. "The TAK-1 inhibitor used in this study is an exciting drug that warrants further development for the treatment of pancreatic cancer."
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