Desarrollos Diagnósticos y Terapéuticos Innovadores en Tumores Sólidos
NATIONAL PROJECTS
Genomic and functional characterization of VEB+/IMS+ gastric cancer
| Funding agency | ISCIII | Amount | 98.615€ |
| PI | Gloria Ribas | ||
| Duration | 01.01.2017 – 31.12.2019 | ||
| Abstract | This project focusses on genomics and functional characterization of subtypes of gastric cancer, VEB + (having infection of the Epstein-Barr virus) and IMS (with microsatellite instability) in patients with gastric cancer. We aim to identify the molecular subtypes from a retrospective serie of 220 tumors between 2003-2013 to those of 2014-2018 that will be added, whose estimate is about 100 additional individuals. Both groups represent between 25-32% of gastric cancer. So we hope to have about 60 tumors IMS+ and 30 VEB +. We will explore the frequent genomic abnormalities (expression, somatic mutations and hypermethylation) in these two subtypes to delve into the specific mechanisms of carcinogenesis and will transfer the findings to cellular models to use these to understand the induced pathogenic mechanisms and search for treatments aimed against them. We will focus on the loss of ARID1A (early event in the development of gastric cancer) and the role of resistance to adaptive immunity. We will evaluate different markers of the immune system in tumor tissue as well as peritumoral infiltrate of lymphocytes and normal adjacent tissue. Further, we will relate how detected genomic alterations induce a “immune checkpoint blockade”. |
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From cancer genomics to immuno-oncology. Identification of responsive biomarkers to anti PD1-PDL1 immunotherapy in cancer through a system biology approach.
| Funding agency | ISCIII | Amount | 98.615€ |
| PI | Joan Climent | ||
| Duration | 01.01.2017 – 31.12.2019 | ||
| Abstract | The development of cancer immunotherapy has reached an important inflection point in the history of cancer therapy. Immunotherapy has shown significant potential for a more targeted approach to treating cancer by harnessing the body’s immune system to fight tumor cells. Based on emerging results it is reasonable to consider that there are many intersections between genetic and immunologic events in cancer, and it may be crucial to identify a biomarker to predict the response to immunotherapeutic agents. Currently, the overexpression of PD-L1 is the one accepted and widely-explored predictive biomarker for the response to antiPD-1/PD-L1 therapy. The question of whether expression of PD-L1 correlates with treatment outcomes has been addressed in most of the pivotal trials, but the answer is still unclear. Gene analysis has proven to be new approach for judging the potential clinical benefit of immune checkpoint inhibitors. Identification of genetic factors that influence the tumor immunophenotype is essential to improve the effectiveness of immunotherapy. These data highlight the need for novel approaches to integration of large data sets including clinical and molecular genetic information to predict individual treatment responses or survival. Here, we propose to perform FISH-analysis targeting PDL1 gene and to compare those results with the PDL1 expression assessed by at least two different antibodies in the same tissues to monitor patients under anti PD-L1 therapy, to develop predictors based on combinations of gene copy number and gene expression changes from previous publish data and to validate them both in DNA and Tissue Micro Arrays from paraffin embedded tumors. Identification of the specific genes involved in determination of cancer sensitivity to anti-PD1 therapies will provide valuable information regarding the dynamic nature of the immune response and regulation of additional combinatorial therapies that may provide survival benefit for greater numbers of patients. | ||
Enfermedad mínima residual en cánceres colorrectales de alto riesgo resecados. Valor de las biopsias líquidas en el seguimiento y análisis de la heterogeneidad tumoral (PI15-02180).
| Funding agency | ISCIII | Amount | 80.465€ |
| PI | Andrés Cervantes | ||
| Duration | 01/01/2016 – 31/12/2018 | ||
| Abstract | Circulating tumor free DNA (ctDNA) in plasma of patients with solid tumors may allow the study of the mutational profile, avoiding surgical or invasive procedures to access tumor tissue. The term liquid biopsies includes the analysis in plasma of any product produced by the tumor, including circulating tumor cells and microRNAs. ctDNA has been studied to determine tumor burden, response to therapies or mechanisms of resistance to some biological agents. This technique also allows the molecular characterization of tumors to define their sensitivity to targeted therapies. This project proposes a longitudinal study in colorectal cancer patients resected with curative intent, but with a high risk of relapse. The first aim is to define the role of liquid biopsies in determining tumor burden at diagnosis. The second aims at monitoring liquid biopsies during follow up to analyze minimal residual disease. The third plans a tumor heterogeneity analysis through the study of potential clonal evolution. A modified Illumina panel TruSight Tumor will be used to detect the presence of molecular abnormalities of colon cancer in plasma. This panel contains the following genes: APC, ARID1A, BRAF, CTNNB1, EGFR, ERBB3, FAM123B, FBXW7, FOXL2, HRAS, NRAS, KRAS, SAMD2, SMAD4, PTEN, P53, PI3KCA and RCF7L2. |
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Ensayo fase III multicéntrico randomizado de radioterapia de curso corto seguido de quimioterapia preoperatoria prolongada y cirugía en cáncer de recto localizado de alto riesgo frente a quimioradioterapia estándar (EC11-423)
| Funding agency | Ministerio de Sanidad y Consumo | Amount | 32.451€ |
| PI | Andrés Cervantes | ||
| Duration | 01/01/2012 – 22/10/2012 | ||
| Abstract | |||
Development of personalised anti-cancer therapy for solid tumour patients whose cancers harbour somatic PTPN11 mutations
| Funding agency | INCLIVA | Amount | 2.000€ |
| PI | Andrés Cervantes | ||
| Duration | 01/01/2014 – 31/12/2014 | ||
| Abstract | |||
Clinical Research and Trials Platform
| Funding agency | ISCIII | Amount | 65.550€ |
| PI | Andrés Cervantes | ||
| Duration | 01/01/2014 – 31/12/2014 | ||
| Abstract | |||
Nuclear heterogenous riboprotein (hnRNPs) hyperacetiliation as a final pathway of anti-EGFR drug resistance in colorectal cancer (PI12/02767)
| Funding agency | ISCIII | Amount | 74.415€ |
| PI | Andrés Cervantes | ||
| Duration | 01/01/2013 – 31/12/2015 | ||
| Abstract | |||
Resistance mechanisms to EGFR inhibitors. Epigenomic and protein acetylation study in wildtype/mutated KRAS cell lines, evaluation in colon cancer patient (PI04/02480)
| Funding agency | ISCIII | Amount | 92.565€ |
| PI | Andrés Cervantes | ||
| Duration | 01/01/2010 – 31/12/2012 | ||
| Abstract | |||
Impact of genetic susceptibility and solar exposition on vitamin D levels in melanoma patients.
| Funding agency | ISCIII | Amount | 98.000€ |
| PI | Gloria Ribas | ||
| Duration | 01/01/2010 – 31/12/2012 | ||
| Abstract | |||
Massive genotyping to genetic characterization of sporadic cutaneous melanoma patients in Spanish population (SAF2009-07072-E)
| Funding agency | MICIIN | Amount | 35.000€ |
| PI | Gloria Ribas | ||
| Duration | 01/01/2010 – 31/12/2010 | ||
| Abstract | |||
Massive genotyping to genetic characterization of sporadic cutaneous melanoma patients in Spanish population (SAF2007-65542-C2-01)
| Funding agency | MICIIN | Amount | 147.000€ |
| PI | Gloria Ribas | ||
| Duration | 01/12/2007 – 03/05/2009 | ||
| Abstract | |||
Massive analysis of SNPs in low penetrance and low breast cancer susceptibility genes.
| Funding agency | MICIIN | Amount | 117.000€ |
| PI | Gloria Ribas | ||
| Duration | 31/12/2004 – 30/12/2007 | ||
| Abstract | |||
Proteomic and metabolomic analysis of irradiated lymphocytes as predictive factor in breast cancer diagnostic (PI041064)
| Funding agency | ISCIII | Amount | 65.895€ |
| PI | Andrés Cervantes | ||
| Duration | 01/01/2004 – 31/12/2006 | ||
| Abstract | |||
Study of breast cancer association with BRCA1/BRCA2 polymorphisms and BRCA1/BRCA2 transcriptional function modulators genes (FIS 01/0024-05)
| Funding agency | ISCIII | Amount | € |
| PI | Andrés Cervantes | ||
| Duration | 01/01/2001 – 31/12/2003 | ||
| Abstract | |||
Diagnostic of inheritance breast cancer predisposition: mutational analysis of BRCA1/BRCA2 genes in early breast cancer Spanish women (FIS 97/0839)
| Funding agency | ISCIII | Amount | € |
| PI | Andrés Cervantes | ||
| Duration | 01/01/1998 – 31/12/2000 | ||
| Abstract | |||