by Comite Web | Nov 16, 2022
In our recently created group we study PDAC tumor stem cells from a personalized medicine approach in close collaboration with clinicians from the Hospital Universitario Son Espases (HUSE). The presence of tumor stem cells with the capacity to regenerate the tumor after resection and adjuvant treatment appears to be a key factor in the poor prognosis of patients with PDAC. However, the oncogenic signaling pathways that maintain these tumor stem cells are poorly understood, a fact that hinders the development of better treatments.
Our interests focus on the study of oncogenic signaling and the microenvironment/microbiome on PDAC tumor stem cell biology and their resistance to treatment. To this end, we use CRISPR gene editing and other advanced gene editing methods on patient-derived organoids generated in collaboration with the Peritoneal Oncologic Surgery Unit (HUSE) and on cell lines.
In addition, we wanted to contribute to COVID19 research by applying our knowledge to study host factors involved in increased susceptibility and severity to COVID19 using lentiviral pseudovirus models and gene editing of primary cultures.
The main lines of research of the group are:
- Study of oncogenic addiction in PDAC tumor stem cells by gene editing.
- Personalized/predictive medicine using patient-derived organoids: Predicting the spectrum of patient response to adjuvant chemotherapy in PDAC.
- Study of mechanisms of resistance to adjuvant treatment in PDAC using patient-derived organoids. Study of the intratumoral microenvironment/microbiome.
- Study of host factors involved in susceptibility to infection by different SARS-Cov-2 strains.
- Identification of predictive biomarkers of susceptibility to SARS-Cov-2 infection.
by Comite Web | Nov 16, 2022
At the CNIO’s Metabolism and Cell Signaling laboratory we study the connection between nutrient excess and cancer. In particular, pancreatic cancer has a strong association with an elevated body mass index, and we still largely do not know why this association exists. Using mouse models, together with biochemical and cellular tools, our group focuses on understanding how overweight leads to aberrant activation of the immune system, chronic inflammation and cellular alterations in the pancreatic epithelium favor cancer development.
by Comite Web | Nov 16, 2022
The vision and mission of the Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), is to achieve personalized cancer prevention. Although we participate in projects on different cancers, our interests are focused on pancreatic and urinary bladder cancer. The scope of the research carried out by the Group ranges from the identification of etiological agents and mechanisms, to the translation of the findings for cancer prevention in the general population and for the clinical management of patients. We apply a wide variety of data, biomarkers, images and omics (molecular big data) that, in combination with state-of-the-art analytical tools and data integration methods allow us to identify risk factors, characterize genetic susceptibility patterns and cancer subtypes and, thus, define the population at risk of developing these cancers. In addition, we are involved in the evaluation of clinical and public health strategies for cancer control using genomic data.
by Comite Web | Nov 16, 2022
The work of our group focuses on three objectives:
1. To identify the mechanisms that contribute in early stages to the development of pancreatic cancer. To this end, we use genetic mouse models that recapitulate human disease and focus on analyzing the role of cell differentiation processes and control of inflammation.
2. To characterize the transcriptional regulatory programs involved in the phenotypic heterogeneity of pancreatic tumors, with a special emphasis on the control of the “classical” and “basal” programs. To this end, we used a combination of approaches including genetic mouse models of pancreatic cancer, human tumor organoids and cell lines.
3. To identify new prognostic and/or predictive markers that may be useful for the management of patients with pancreatic cancer. These studies use samples of patients with pancreatic cancer from various collaborative studies, mainly with Núria Malats’ group but also with various international groups.
by Comite Web | Nov 15, 2022
The Experimental Oncology Group of the Spanish National Cancer Research Center focuses its research on identifying therapeutic strategies against pancreatic and lung tumors induced by the KRAS oncogene. For this purpose, we use genetically modified experimental mouse models that closely reproduce the natural history of the corresponding human tumors. In the case of pancreatic tumors, four years ago we published that deletion by genetic manipulation of two targets involved in signal transmission of the KRAS oncogene, RAF1 kinase and the epithelial growth factor receptor, EGFR, induced complete regression of a percentage of such tumors (Blasco et al., Cancer Cell, 2019. PMID: 30975481).
These studies demonstrated for the first time that it was possible to eliminate pancreatic ductal adenocarcinomas by inhibiting two targets involved in KRAS signaling, although most of the tumors that responded to this therapeutic strategy were smaller tumors. Since then, the work of our laboratory has focused on (i) identify additional targets that, in combination with RAF1 and EGFR deletion, will allow us to achieve the elimination of all, or at least a large majority, of pancreatic tumors induced by the KRAS oncogene regardless of their size or stage without causing significant toxic effects and (ii) in pharmacologically validating these therapeutic strategies by using selective inhibitors against these targets either alone or in combination with the recently identified KRAS inhibitors, with the ultimate goal of being able to transfer these results to cancer patients.
