Cancer is our primary focus, as therapy failure remains a major clinical challenge. Many patients experience limited benefit or relapse due to drug resistance, tumor heterogeneity, or severe toxicities. These limitations highlight the urgent need for strategies that are both more effective against tumors and safer for patients.

Our research seeks to uncover molecular mechanisms of drug sensitivity and resistance, identify predictive biomarkers, and reveal new therapeutic vulnerabilities. While our main focus is genitourinary cancers, particularly kidney tumors, we also investigate germline variants that predispose to drug toxicity, supporting the development of personalized therapies. We integrate cellular and animal models, multi-omic profiling, and clinical expertise to accelerate translation into practice.

1) Molecular stratification of kidney cancer
Our goals are to identify molecular alterations in renal cell carcinoma (RCC) that define tumor molecular subgroups with clinical relevance for drug response to key therapies —including antiangiogenic drugs, immune checkpoint inhibitors, and mTOR and HIF2a inhibitors— and to propose novel therapeutic approaches. To achieve this, we use large tumor collections and in vitro/in vivo models.

In clear cell RCC histology, we have pioneered findings showing how crosstalk between alterations influences therapy response, and how germline variation modulates drug effects on the tumor microenvironment. We also identified somatic mutations, gene expression signatures, and microRNAs as predictive/prognostic biomarkers (e.g., Lancet Oncol 2011; Ann Oncol 2013; JCI Insight 2016; Int J Cancer 2020; Eur Urol 2022). Current efforts focus on how mutations in chromatin remodelers reshape the transcriptome and affect antiangiogenic or immunotherapy response, with emphasis on sex-specific effects.

In other RCC subtypes, we study how Krebs cycle gene alterations (FH, SDHB, L2HGDH) lead to oncometabolite accumulation, pseudohypoxia, and epigenetic remodeling, especially in papillary RCC (bioRxiv 2025). In chromophobe RCC, we identified the mTOR pathway as a determinant of aggressive disease (Mol Path 2020), and continue to define biomarkers and vulnerabilities (Int J Cancer 2023). We also refine treatments for hereditary RCC syndromes (e.g., VHL disease, HLRCC) in collaboration with clinical groups and patient associations.

2) Novel biomarkers in genitourinary and other tumors
Beyond kidney cancer, we study biomarkers of cancer susceptibility, aggressiveness, and resistance in other tumor types. These projects, based on multi-omic technologies, are supported by national and international consortia (GUARD, Grupo Germinal Oncológico, OCAC/OTTA). Together with Grupo Germinal, we currently lead a study to identify cisplatin resistance biomarkers in testicular germ-cell tumors.

3) Germline pharmacogenetic markers of drug toxicity
We have extensive experience identifying genetic risk factors for chemotherapy-induced toxicities. Our work uncovered germline variants associated with paclitaxel-induced peripheral neuropathy (Clin Cancer Res 2012–2017; J Med Genet 2013) and clarified the role of concomitant medications (Oncologist 2019). We also pioneered the use of whole-exome sequencing to discover pharmacogenetic markers of toxicity (NPJ Genom Med 2022; Genet Med 2018). Currently, we investigate the toxicity of the antibody–drug conjugate trastuzumab deruxtecan, combining candidate-gene and hypothesis-free approaches such as GWAS.

Leadership and impact
The research led by Cristina Rodríguez-Antona places her among the world’s most highly cited scientists, with more than 160 scientific articles and an h-index of 51 (ISI Web of Science). These advances have only been possible through an interdisciplinary team with expertise in molecular biology, genomics, and translational oncology, supported by large annotated tumor collections and a strong network of clinical collaborators and patient associations.

Our research projects are organized into four main areas and are detailed below, along with an overview of our team and acknowledgments.