Researchers identify potential biomarkers predictive of TKI response in metastatic kidney cancer

Researchers identify potential biomarkers predictive of TKI response in metastatic kidney cancer -

A team of CNIO researchers, in collaboration with the Spanish Oncology Genitourinary Group (SOGUG ) and University Hospitals of Leuven (Belgium), discovered various predictive potential biomarkers of tyrosine kinase inhibitors (TKIs) response in metastatic kidney cancer. In their study, published in JCI Insight , researchers identify various miRNAs that define a group of patients refractory to TKI type of anti-angiogenic agent widely used to treat kidney carcinoma- processing cells -a and with a poor prognosis. The study, conducted on 139 patient samples, is the most robust to date in this type of tumor.

Finding biomarkers that can help determine the prognosis of a patient, the risk of recurrence or, as in this case, their sensitivity to various drugs will enhance personalized treatment for these patients

Although there are dozens of biomarkers predictive drug response in cancer, there are none for metastatic renal cell carcinoma, or for his standard treatment. antiangiogenic agents, which doubled the median overall survival of patients since their approval a decade ago.

However, not all patients show a positive response. "There is a group of patients who are refractory to this therapy," says Cristina Rodríguez-Antona, the Hereditary Endocrine Cancer Group at the CNIO. "This means that the tumor will continue to grow in the presence of EGFR." At present, there is no way of knowing how each patient will respond, but "if we could know in advance, we could apply the most appropriate treatment, "said the researcher.

STABLE DETECTABLE Molecules

Immersed in biomarker research, the team found that the miRNA would be good candidates. These small molecules act as regulators in several biological processes Programmed cell death, proliferation and differentiation, for example-and they are also very stable, which facilitates preservation in tissue samples.

as the first approach, the authors conducted in-depth sequencing of miRNAs in samples from 74 patients treated with TKIs. of these, 16 (22%) have already shown the progression of the disease in the first control, while in 58 (78%) of the tumor presented complete or partial response to treatment or disease stabilization.

After several tests and adjustments, of the 65 miRNAs whose expression was significantly different in the early progressive tumors versus stable, six appeared to be "easily detectable biomarkers" and were selected for independent validation . Five of them were still associated with poor response to ITK and appeared to be independent of the patient's prognosis.

PREDICT GOOD MODEL

"The next-generation sequencing has enabled us to detect all miRNAs in a large cohort enough [of patients]," says Rodríguez- Antona. "to date, -She explains- other studies have used small series and less robust techniques and, therefore, the results have been limited."

To reinforce this first observation, the authors generated a predictive model in a group of 132 patients. First, they considered the five miRNAs differentially expressed, in addition to other clinical features (prognostic group, age, sex ...) and, after several analyzes, they identified a model based on two miRNAs that showed "a greater accuracy than any tested clinical factor", with regard to the prediction of how the tumor respond to treatments based TKI.

With the advent of new drugs and the various responses displayed by patients, "we'll need biomarkers to guide treatment decisions," says Rodríguez-Antona. This article shows that miRNAs are good predictors of response to TKIs. Although the researchers point out that "these results should be validated in other series of patients before using them to customize treatments for metastatic kidney cancer."