Endocrine tumors constitute a set of neoplasms originated in organs of the endocrine system, including thyroid cancer (differentiated, medullary and anaplastic), neuroendocrine neoplasms of gastroenteropancreatic and pulmonary origin, adrenal carcinoma, paraganglioma, pheochromocytoma and Merkel cell carcinoma. Low incidence and heterogeneity has delayed the evolution of the molecular profiles that allow the clinical development of targeted therapies, and there is an unmet need of experimental models to investigate new therapies against endocrine neoplasms. Our multidisciplinary group at the Vall d´Hebron Institute of Oncology (VHIO) in collaboration with the Vall d´Hebron University Hospital have already established the necessary circuits for the generation of the “Patient-Derived Xenografts” (PDX) models in the endocrine tumors setting. Recently we have successfully generated several models derived from colorectal neuroendocrine, thyroid and adrenal cancer. These models have been useful to carry out experiments to explore efficacy and mechanisms of resistance to BRAF and RET-inhibitors in BRAF V600E and RET fusion driven tumors. In the present project, we aim to study the potential mechanism of acquired resistance to RET-inhibitors and the comparison of new specific RET inhibitors (LOXO-292 and BLU-667) with current approved multikinase inhibitors in thyroid cancer setting. Additionally, we will explore the same approach for other endocrine malignances (such as neuroendocrine tumors of the gastrointestinal tract, lung and Merkel cell carcinoma) where RET alterations have been described using the stablished and new PDX models from patients with endocrine tumors.

Neoplasias Endocrinas
Cáncer de Tiroides
Tumores Neuroendocrinos
Modelos Murinos
Inhibidores de RET
Perfiles moleculares
Cáncer