BIOMARK: Searching for molecular biomarkers associated with cancer progression and treatment

Inicio Investigación Grupos de Investigación BIOMARK: Searching for molecular biomarkers associated with cancer progression and treatment
MJ_JPG
Dra. Maria Jesus Alvarez Cubero

Principal Investigator

General information

Scientific areas of interest

Scientific interest areas

Precision medicine aims to eliminate the current «one size fits all» model of patient management, which generalizes treatments, and replace it with a new model that adapts to the individual biology of the disease. Personalized medicine and pharmacogenetics allow us to know the evolution of different pathologies and to determine the response to different drugs in advance.

Following this objective, this multidisciplinary group, formed by basic and clinical researchers, was born, a synergy that began more than 10 years ago as a result of the need to incorporate genetic markers into clinical practice. This collaboration has made it possible to combine knowledge in molecular genetics and the identification of genetic biomarkers in daily clinical practice, especially for the application and dosage of pharmacological treatments.

This group focuses its efforts on two fundamental objectives. On the one hand, to describe new genetic variables that serve as biomarkers to predict the risk of appearance or evolution of different diseases. On the other hand, to study the response to drugs, including essential factors such as efficacy and safety. To achieve these purposes, our group uses the omics sciences: genomics, transcriptomics and epigenomics.

Individualized medicine requires the identification, characterization and evaluation of genetic biomarkers, which we approach by studying changes in the genome and variations in gene expression or its regulatory elements. It is also essential to determine all the components involved in the onset of the pathology, its evolution and its response to treatment, without forgetting the patient’s lifestyle and environment. Only by controlling all these clinical, personal and environmental variables, what we call massive phenotyping, will we be able to understand the complex biological network of multifactorial diseases.

Social and scientific impact:

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 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.

Lines of research

Research Line 1: 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.

Research Line 2: 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.

Line 3: Identification of genetic markers associated to drugs used in prostate 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.

Funding

  • Ministerio de Ciencia e Innovación.
  • ISCIII-CDTI.
  • ADAMED Laboratorios SLU.
  • European Commission (HORIZON 2020).
  • Consejería de Universidad, Investigación e Innovación.
  • Consejería de Salud y Consumo.
  • Consejería de Salud y Familias.
  • European Regional Development Fund (ERDF).
  • European Molecular Biology Organization (EMBO)
  • Fundación para la Investigación en Urología (FIU).
  • Ministerio de Ciencia e Innovación.
  • Ministerio de Economía y Empresa.
  • Oficina de Transferencia de Resultados de Investigación (OTRI) – Plan Propio.
  • Pfizer, Inc.
  • Servicio Andaluz de Salud, Junta de Andalucía.
  • Vicerrectorado de Investigación UGR. – Plan Propio
  • European Food Safety Authority (EFSA).

Technology platforms

  • Genotyping (iSan, Illumina, FLUOstar Omega SNP, Q6 real time, QuantStudio 3D, GeneAmp PCR System 9700, Applied Biosystems).
  • Sequencing (NextSeq 500, MiSeq, NovaSeq).
  • Flow Cytometry and Cell Sorting (CyTOF, FACS Aria, FACS Canto II).
  • Cell Culture and Genomic Editing.
  • Chromatography (HPLC, LC-MS/MS).

Internationalization

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).

Publications

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