A study led by researchers from the Hospital del Mar Medical Research Institute (IMIM), has determined, for the first time, the importance of a cell mechanism that may be key to treating metastatic tumours. The work has demonstrated the role a protein, kinase IKKα, plays in the ability of tumour cells to repair themselves. This is a key factor in treatment resistance and tumour spread. The research has been published in the journal Molecular Cell.

The researchers analysed the role of this protein, activated by mutations of the BRAF and KRAS oncogenes, present in the majority of the most aggressive tumours. The function of this protein is to facilitate DNA-repair in tumour cells after they have been damaged by chemotherapy, making them more resistant to the action of these drugs. This is key for the treatment approach, since this new study demonstrates, conclusively, that combining a BRAF oncogene inhibitor with chemotherapy deactivates and kills the tumour.

These same oncogenes, in addition to converting normal cells into tumours, make them better able to repair the damage caused by chemotherapy agents or radiation, and make them more resistant. In other words, they play a double role, facilitating tumour transformation and protecting the tumour from the damage caused by chemotherapy and radiation. "The presence of these mutations makes treatment very difficult but this is also an advantage, because if, thanks to these mutations, the tumour cell is more resistant to damage, eliminating their activity with drugs that are currently used in clinical practice will make the tumour even more sensitive to the treatments. And that’s what we’ve demonstrated” explain the researchers.