Pharmacogenomics and Tumor Biomarkers

The main interest of the Pharmacogenomics and Tumor Biomarkers Group (@PGx_IIBM) is understanding how genomic variation modifies drug treatment response, with the ultimate goal of using this knowledge to design more specific drug treatments.
In cancer, drug therapy failure is a major clinical problem and developing safer and more effective anticancer drug treatment strategies is urgently needed. Our top priority is improving the survival and quality of life of cancer patients. To this end, we focus on the discovery of new mechanisms of drug sensitivity/ resistance, the identification of biomarkers predictive of treatment response, and proposing novel cancer therapeutic vulnerabilities. The identification of germline genetic variants that increase the risk of drug toxicity is also a fundamental part of our objectives. To achieve these goals, we perform translational research that integrates genomics and bioinformatics with the clinical expertise of oncology departments.
Our objectives are:  

1) Identifying driver/ secondary mutations able to recognize tumor molecular subgroups with clinical meaning for drug response 
Our work is mainly in (but not limited to) renal cell carcinoma (RCC) and its central therapies: antiangiogenic drugs, immune checkpoint inhibitors, HIF2a inhibitors. In clear cell RCC histology, we focus on understanding the role of mutations in chromatin remodelers, using large collections of tumor/ samples and in vitro/ in vivo models. In other RCC histologies, Krebs cycle alterations leading to oncometabolite accumulation and pseudohypoxia are essential parts of our research.

2) Defining prognostic biomarkers and new tumor vulnerabilities. 
Specifically, we are interested in novel treatment targets and indicators of aggressive disease in sporadic genitourinary cancers, hereditary kidney cancer (e.g. VHL disease and Hereditary leiomyomatosis and renal cell carcinoma) and ovarian cancer.

3) Discovery and validation of germline pharmacogenetic markers of drug toxicity. 
Based on our previous experience in drug-induced peripheral neuropathy, we are studying the toxicity of antibody-drug conjugates such as trastuzumab deruxtecan, using candidate gene approaches and hypothesis-free strategies such as Genome Wide Association Studies (GWAS). In addition, to boost the clinical implementation of pharmacogenetics we explore the repurposing of NGS data to extract well-known pharmacogenetic markers.

This research is supported by an interdisciplinary team with expertise in high-throughput genomic technologies, access to large tumor/sample collections with clinical annotation, and active collaboration with clinical groups and patient associations (e.g. Spanish VHL disease Alliance). Previous contributions from our group include: identification of germline and somatic alterations associated with antiagiogenic drug response in renal cancer (Lancet Oncology, Ann Oncol, JCI Insight, Eur Urol); discovery of germline variation leading to increased risk of paclitaxel-induced peripheral neuropathy (Genet Med, Clin Can Res); repurposing of whole exome sequencing data to extract/ discover pharmacogenetic toxicity markers (NPJ Genom Med, Genet Med); identification of novel cancer susceptibility, prognostic and predictive biomarkers through omic technologies (Nature Genetics, Genet Med).

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Metabolic and Immune Diseases

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Neurological Diseases and Aging

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Rare Diseases

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