Integration of omics data for the search for molecular biomarkers associated with urological cancers

The study of urological includes tumors as frequent as prostate or bladder cancer and others, less frequent but more aggressive such as kidney cancer. We combine the main omic techniques to search for biomarkers in solid tumors (in paraffined tissue and by Single Cell analysis in fresh biopsies) and liquid biopsy. Using nextgeneration sequencing (NGS), we can reach a complete vision of the genetic panorama of each patient, unmasking biomarkers that enable the stratification of patients early and precisely based on their future aggressiveness, prognosis or response to treatment. Thus, using non-invasive techniques the detection of these biomarkers will mean a change in the treatment approach towards personalized and precision medicine.

The combination of environmental exposures (exposome) provides a new approach to the etiology of cancer. The health effects of these exposures events depend on genetic factors such as genes encoding xenobiotic-metabolizing enzymes (XME) and antioxidant defense enzymes. However, the metabolic pathways in which these enzymes are involved are not well studied in cancer and it has not been established a clear relationship between the different isoforms with cancer aggressiveness. Currently, the group is focused on the evaluation of different genetic factors in urological cancers and their association with the exposome by means of questionnaires and biomonitoring. This combination can contribute to the detection of biomarkers of exposition necessary for the personalization of prevention and treatment depending on the environment of each patient.

I currently collaborate with the following laboratories: J.A Lorente Lab bringing my liquid biopsy expertise to my non-invasive biomarker searching. Moreover, we have sporadic collaborations with E.Carnero from M. Alarcón´s lab in COVID-19 analysis of samples and J.Sainz in a cohort of prostate cancer samples.

The main scientific impact of present lines and projects are focused on not only the discovery of biomarkers for screening or stratification. We go a step forward 76 STRATEGIC PLAN 2024-2027 integrating their biological impact, search for metabolic pathways that alter these markers and managing how treatment affects different clusters of biomarkers (and patients). Each of these genetic positions will be investigated as a potential target for new drugs.

Over the past three years, we have invested significant resources in building a network of urologists who have enrolled approximately 1,000 prostate cancer patients. Tissue biopsies (fresh and FFPE), blood and urine samples are available for 40% of patients. In addition to the biological samples mentioned above, we also have a longitudinal record of personal, clinical and environmental data.

We are also conscious about the high social impact of some urological diseases, mainly prostate cancer, and having a better knowledge and classification would help to improve quality of life of these patients. Currently, even being one of the most frequent malignancies among men, there is still unknown molecular markers in its management. For this reason, we are following our cohort, getting to know our patients and interviewing them frequently. Our basic idea is that massive phenotyping will help to classify the data obtained by massive genotyping.

We are part of the international prostate cancer consortium (PRACTICAL), which makes it easy to achieve samples and connections with all international groups focused on prostate cancer study. Nowadays, we have a strong collaboration with UK University of St. George´s as active collaborators of Prostate Cancer Research team based at St. George’s, University of London in charge of Clara Cieza and Ferran Valderrama (University of St. George´s, London, UK), where we are currently developing experiments in spheroids and organoids in prostate cancer (derived from prostate patients of our collection).

Although we are conscious of the difficulty of achieving European funding, this will lead us to try this opportunity in the next years. Afterwards, we keep on having an active funding capture of public Spanish institutions, such as recently funded by TRANSMISIONES (ISCIII) with a budget of 950.000 € for a prostate cancer research project.