Descripción del proyecto
Comprensión de las propiedades adaptativas de las células cancerosas en la evolución de la enfermedad
La composición y las características moleculares de los tumores cambian en el curso de la enfermedad, pero los mecanismos subyacentes a estos cambios aún no se comprenden bien. El proyecto CancerADAPT, financiado con fondos europeos, se basa en el postulado de que las células cancerosas dependen de mecanismos transcripcionales y metabólicos adaptativos, por lo que generan rápidamente nuevos microentornos durante la evolución de la enfermedad. El proyecto aspira a predecir los estímulos moleculares que rigen las propiedades adaptativas de las células del cáncer de próstata (CP). Los investigadores utilizarán la secuenciación de ARN de células individuales, la transcriptómica espacial y la ómica multirregional para identificar la diversidad transcripcional y metabólica dentro de los tumores en el curso de la enfermedad. Los análisis computacionales les permitirán identificar y clasificar las estrategias de adaptación predichas de las células del CP en respuesta a las variaciones en el microentorno del tumor.
Objetivo
The composition and molecular features of tumours vary during the course of the disease, and the selection pressure imposed by the environment is a central component in this process. Evolutionary principles have been exploited to explain the genomic aberrations in cancer. However, the phenotypic changes underlying disease progression remain poorly understood. In the past years, I have contributed to identify and characterise the therapeutic implications underlying metabolic alterations that are intrinsic to primary tumours or metastasis. In CancerADAPT I postulate that cancer cells rely on adaptive transcriptional & metabolic mechanisms [converging on a Metabolic Phenotype] in order to rapidly succeed in their establishment in new microenvironments along disease progression. I aim to predict the molecular cues that govern the adaptive properties in prostate cancer (PCa), one of the most commonly diagnosed cancers in men and an important source of cancer-related deaths. I will exploit single cell RNASeq, spatial transcriptomics and multiregional OMICs in order to identify the transcriptional and metabolic diversity within tumours and along disease progression. I will complement experimental strategies with computational analyses that identify and classify the predicted adaptation strategies of PCa cells in response to variations in the tumour microenvironment. Metabolic phenotypes postulated to sustain PCa adaptability will be functionally and mechanistically deconstructed. We will identify therapeutic strategies emanating from these results through in silico methodologies and small molecule high-throughput screening, and evaluate their potential to hamper the adaptability of tumour cells in vitro and in vivo, in two specific aspects: metastasis and therapy response. CancerADAPT will generate fundamental understanding on how cancer cells adapt in our organism, in turn leading to therapeutic strategies that increase the efficacy of current treatments.
Ámbito científico
Palabras clave
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
48160 DERIO VIZCAYA
España