2023-06-14 13:40:07
15 years ago, a woman in her thirties was diagnosed with metastatic kidney cancer. the oncologist Jose Pablo Marotofrom the Hospital de la Santa Creu i Sant Pau, in Barcelona, decided to treat her with the drug temsirolimus, which worked better than expected, so the patient overcame that cancer. Nine years later, a bone metastasis was detected in the same patient, and also in this case the temsirolimus.
Maroto together with researchers from the National Cancer Research Center (CNIO) studied why this drug was so effective in this case and in that of two other people and now they explain it in an article published in the International Journal of Cancer.
The finding will make it possible to identify other patients with kidney cancer for whom the temsirolimus and other drugs of the same family will, with great probability, be the ideal treatment. These are compounds —mTOR pathway inhibitors— that, up to now, have only been used when others fail.
This finding will make it possible to identify other patients with kidney cancer for whom temsirolimus will be the ideal treatment.
“Currently, the drugs of the family of temsirolimus They are not usually the first option 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,” he says. Cristina Rodriguez-Antonaprogram researcher CNIO Human Cancer Genetics.
Find the answer with this work, whose first author is Juan Maria Roldan-Romero, it has taken years, according to the note distributed by CNIO. It was necessary to come up with more Similar cases those of the first patient, for which reason the Sant Pau hospital team selected them and sent their samples to the research center, where they were analyzed in depth.
The key lies in rare mutations in the USP9X protein, which regulates critical cellular processes for tumor growth.
“Why has this treatment worked so well? This is not the first case in which we have asked ourselves this question, but it is one of the first in which we have obtained a clear answer,” explains Maroto.
The key is in some very rare mutations in the USP9X protein, which regulates cellular processes critical to tumor growth. Research shows that mutations knock out the function of USP9X and when that happens the cell doesn’t recycle its waste well and dies. He temsirolimus it acts on a different molecular pathway, but has a similar effect; in patients where USP9X does not work, the impact of this drug is potentiated.
The research was financed in part with donations obtained in solidarity races
Rodríguez-Antona explains: “To understand the effect of mutations in USP9X, we developed cell models and carried out proteomic assays that indicated that tumor cells without USP9X had an alteration in cellular autophagy, which is the process by which the cell recycles its waste products. He temsirolimus it also alters autophagy, which causes a synergistic effect, making tumors more responsive to this treatment.”
A new therapeutic target
In addition to serving to identify other patients with USP9X mutations who could benefit from treatment with drugs from the family of temsirolimusthis finding facilitates the development of new drugs that inhibit this protein as an innovative therapeutic strategy.
“A compound that cancels the function of UPS9X would have a synergistic effect with temsirolimus, increasing its anti-tumor efficacy”, indicates Rodríguez-Antona.
According to the authors, “translational studies are complex because they require close collaboration between clinicians and basic researchers.” In addition, patients play a fundamental role, “donating their samples at a very difficult time.” This study in rare tumors could only be carried out “thanks to the generosity of the patients, whose samples are the basis of all the subsequent molecular work and who promoted the study from its beginning”, as they emphasize in the presentation of the article.
It is also highlighted that the job It was partly financed with donations obtained in solidarity races organized by the Club de Atletisme A 4 el KM, from Les Franqueses del Vallés (Barcelona), promoted by the patient.
Rights: Creative Commons.
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