Oncogenes and Metastasis
The dissemination of cancerous cells from the primary tumor is the most devastating consequence of cancer. A singular characteristic of metastasis is the propensity of the cell to lodge in selected organs, such as the skeleton. Our group attempts to understand how this process is initiated, what makes the bone such a singular target and how the bone microenvironment affects metastatic progression. The ultimate goal is to determine the reciprocal lung-bone interactions that occur in models of epithelial (lung cancer) and mesenchymal (bone sarcoma) origin by using a combination of cell and molecular techniques with sophisticated imaging technology, such as bioluminescence analysis, microCT scans and PET. We are specifically seeking to identify genes that confer a high metastatic potential in lung-cancer models. Our group also seeks to functionally characterize the mechanisms of the carcinogenic and metastatic process in bone tumors. Using a functional genomic approach and microarray technology with tissues in cells and animal models, our work aims to identify key pathways induced in early stages of sarcomagenesis.
In lung cancer and in intestinal-tract tumors such as pancreatic cancer, bowel cancer and cholangiocarcinoma, KRAS is the most widely mutated gene and an undoubted therapeutic target. Nevertheless, KRAS continues to be refractory to targeted therapies and its inhibition is thus an unmet clinical need. Therefore, in the laboratory, we are also very interested in identifying new molecular targets in KRAS-dependent tumors and in discovering innovative therapeutic strategies for treating these tumors. To this end, we've taken a multimodal approach, which includes functional genomic techniques, mouse genetics, in vitro and xenograft models, analysis of human cancer samples, and clinical parameters. Furthermore, the laboratory recently incorporated work with organoids (3-D organ buds) from primary human and murine cells, and from cell lines. This model makes it possible to carry out in vitro and in vivo studies of gene modulation, pharmacological treatments and cell co-cultures. To date, we have carried out innovative computational analyses by integrating databases of patients with lung cancer and pancreatic cancer in which KRAS is mutated, and we have identified new critical elements in these tumors and are actively characterizing them in close collaboration with professionals from the Clínica Universidad de Navarra who have an interest in lung and intestinal-tract tumors.