Meritxell Riera came to hear that her kidney cancer was terminal. had metastases, so he decided to undergo an experimental treatment to improve his quality of life. She not only did it, but she overcame the disease and now, 15 years later, researchers have found that the woman had a rare genetic mutation that enhanced the effect of the drugs they gave her.

A scientific milestone that opens a new horizon to be able to treat other patients. It was discovered by researchers from the National Cancer Research Center (CNIO) and the Sant Pau Hospital in Barcelona, ​​who detected that rare mutations in a protein explained why the patient survived in an extraordinary way. Scientists have discovered that these mutations potentiated the effect of a second-line cancer drug, temsirolimus.

The finding, which will make it possible to address more cases like this patient’s, has required several years of joint research with oncologists from the Hospital de Sant Pau in Barcelona, where the patient was treated, and is now published by the ‘International Journal of Cancer’. Research has revealed that this drug, which is used only when first-line drugs fail, is ideal for those with this mutation.

The investigation began 15 years ago when Meritxell, then in her thirties, was diagnosed with metastatic kidney cancer and the oncologist at Hospital Sant Pau Jose Pablo Maroto decided to treat her with the drug temsirolimus, which worked much better than expected and the patient overcame the cancer, although nine years later a bone metastasis was detected, but this time, too, temsirolimus was effective. This drug, which has also been effective in two other patients, is an inhibitor of the mTOR pathway, and is used only when others fail.

“Currently the drugs of the temsirolimus family are not usually the first choice in kidney cancer, but this result indicates that in some very specific patients, they should be, because they work very well. Now we know how to identify these patients”, explained the CNIO Human Cancer Genetics researcher Cristina Rodríguez-Antona. The research has been financed in part with donations obtained in charity races organized by the Club de Atletisme A 4 el KM, from Les Franqueses del Vallès (Barcelona), promoted by the patient herself.

“This publication is a source of pride. It is a collaboration between an association that organizes year after year a popular race for kidney cancer research, patients who give up samples in difficult times, and basic and clinical researchers. Everything, to answer why has Did this treatment work so well? This is not the first time we have asked ourselves this question.but one of the first in which we obtain a clear answer”, has declared Maroto.

The oncologist has recalled that finding this answer has taken years and that it was necessary to find more cases similar to those of the first patient, which the Sant Pau team selected and sent their samples to the CNIO, where they were analyzed in depth.

Researchers have discovered that the key lies in very rare mutations in the USP9X protein, which regulates cellular processes critical to tumor growth, and they have seen that these mutations abolish the function of USP9X, and when that happens the cell does not recycle its waste well and dies. Temsirolimus acts on a different molecular pathway, but has a similar effect, and in patients where USP9X does not work, the impact of this drug is enhanced.

The researchers developed cell models and did proteomic assays that indicated that the tumor cells without USP9X had an alteration in cellular autophagy, which is the process by which the cell recycles its waste products, so that how temsirolimus also alters autophagycauses a synergistic effect and makes tumors respond better to this treatment.

According to the researchers, in addition to identifying other patients with USP9X mutations, who could benefit from treatment with drugs from the temsirolimus familythis finding supports the development of new UPS9X inhibitor drugs as an innovative therapeutic strategy.