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

Our group emerged thanks to our starts in 2008 where we established a strong connection between clinical gaps (urological tumor) and molecular biomarkers. We realized that current clinical strategies in tumors such as prostate or kidney diseases lack robust molecular panels. In addition, we understood the great tumor heterogeneity that exists in these patients and where omics strategies could provide a direct clinical response. Over the years, our discoveries have led us to realize the role of each molecular markers in cancer development and decode the intricate networks that reshape the genetic structure of cancer in different tissues and cells. We have also explored how environmental factors contribute to tumor formation, considering the exposome and its impact on epigenetic regulators within this complex metabolic network. We focus our strategies on the search for non-invasive markers that could improve patient stratification using different omics integration methodologies.

We are a multidisciplinary group compound by clinical doctors, clinical pharmacist, biologists and informatician. Most of the group is affiliated to the Department of Biochemistry and Molecular Biology III and Inmunology of the University of Granada, Urology and Hospital Pharmacy Service from “Universitary Virgen de las Nieves Hospital”. Thanks to the multidisciplinary activity, currently we account for approximately 1,000 prostate cancer samples (tissue biopsies (fresh and FFPE), blood and/ or urine). In addition to the biological samples mentioned above, we also have a longitudinal record of personal, clinical and environmental data.

Moreover, 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).

What is the molecular basis of epigenetic memory?

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

The study of urological tumors includes those as prostate or bladder cancer; but also, other less frequent but more aggressive such as kidney cancer. We combine the main omic techniques for searching biomarkers in solid tumors (in paraffined tissue and by Single Cell analysis in fresh biopsies) and liquid biopsy. Using next-generation sequencing (NGS), we can reach a whole 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.

• Role of genetic variants in xenobiotic metabolic enzymes in cancer. Gene-environment interaction through exposome analysis:

The combination of environmental exposures (exposome) provides a new approach to the etiology of cancer. 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 tumors and their association with the exposome by integrating questionnaires and biomonitoring. This combination can contribute to the detection of biomarkers of exposition useful for personalized prevention and treatment based on the environment of each patient.

• Identification of genetic markers associated to drugs used in cancer and functional validation

About -15-20% of all hormonal treated patients stop responding to treatment and in around 3 years they progress to treatment resistant (CPRC). Therefore, our group aims to identify genetic markers that will explain such unresponse effects to drugs (Goserelina, ⁠Leuprorelina,Triptorelina, ⁠Histrelina, Abiraterona, ⁠Enzalutamida, Apalutamida and Darolutamida). Moreover, we will develop in vitro functional validation of them to try to include these variants as biomarkers in the clinical daily practice.

Related Biography of the group research line: