Drugs that regulate fatty acid metabolism could help in the treatment of pancreatic cancer in combination with chemotherapy

Recently, the Journal of Translational Medicine has published the article «Fatty acid oxidation is critical for the tumorigenic potential and chemoresistance of pancreatic cancer stem cells» by Marta Mascaraque, researcher of the IIS Aragón 'Metabolism & Cancer Stem Cells' group

El pancreatic cancer It is the tumor with the lowest survival rate. Its aggressiveness is due in part to a type of cell called tumor stem cells, which are capable of resisting current treatments and generating new tumors. For this reason, it is especially important to find treatments capable of eliminating this type of cell.

The IIS Aragón group 'Metabolism & Cancer Stem Cells', led by Patricia Sancho, seeks strategies with which toattacking pancreatic cancer stem cells. Precisely, these days the Journal of Translational Medicine has published the article «Fatty acid oxidation is critical for the tumorigenic potential and chemoresistance of pancreatic cancer stem cells» by Marta Mascaraque, researcher of the IIS Aragón group 'Metabolism & Cancer Stem Cells'. 

Cancer stem cells need a greater supply of energy to maintain their increased proliferation, so their energy-obtaining mechanisms, i.e. their metabolism, are different from those of healthy cells. Because of this difference, one of the strategies to attack pancreatic cancer stem cells is to attack their metabolism. In this sense, Dr. Sancho's team has demonstrated in laboratory models that inhibiting fatty acid metabolism is a promising strategy against tumor proliferation and preventing resistance to chemotherapy.

Los investigadores They have confirmed that pancreatic cancer stem cells accumulate greater amounts of fat and have a more active metabolism, all in order to obtain more energy.a. They then demonstrated that inhibiting the process by which cells metabolise this fat (known as fatty acid oxidation) reduces the tumour-causing capacity of pancreatic cancer stem cells. On the contrary, an extra supply of fatty acids increases the tumour-causing capacity of cells. Therefore, fatty acids and their metabolism are a key element in the progression of cancer and are presented as a promising therapeutic target on which to act with new drugs. This research team has also demonstrated that the efficacy of chemotherapy is increased by combining it with drugs that inhibit fatty acid metabolism. This greater efficacy is due to the fact that the inhibition of fatty acid metabolism helps to avoid chemotherapy-associated resistance in pancreatic cancer stem cells. It should be noted that several of these drugs (such as ranolazine) have already been approved for use in humans for the treatment of other diseases, which could speed up their application, although further studies are still necessary.

Although these results are promising, the researchers from the group emphasize that further research is needed to demonstrate that this combination treatment is safe and effective in mice with a complete immune system before moving on to testing it in patients.

In addition, this article has been published with the results corresponding to two grants from the Spanish Association Against Cancer that the group has obtained: AECC Worldwide (in collaboration with Worldwide Cancer Research) and LAB AECC. 

• Investigation article: https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-05598-6