Université de Strasbourg

Neuroendocrine tumors

Molecular mechanisms of hyper-secretion in neuroendocrine tumors

USIAS Fellow : Laurent Brunaud et Stéphane Gasman

Neuroendocrine tumors, a heterogeneous group of tumors arising from hormone-secreting cells, are generally associated with a dysfunction of secretion. While this aspect is well known by the clinicians, the underlying mechanisms have never been explored at the cellular level. The aim of this project is to uncover the molecular and cellular mechanisms responsible for hyper-secretion in neuroendocrine tumor. To achieve this objective, we will combine the highly sensitive amperometry technique with quantitative proteomic analysis on human tumors originating from adrenal medulla chromaffin cells (pheochromocytoma) or from digestive enterochromaffin cells (small intestine, midgut).

Today, neuroendocrine tumors are clearly underserved by targeted therapies either than surgery, which limits the possible interventions and reduces patient survivability. An interesting line of thought, that has never proposed so far, is to consider secretion as a potential target. It is of enormous significance since anarchic secretion of neuroendocrine tumor cause serious illness and complications and appears directly related to the aggressiveness of the tumor. Through this original approach, we are expecting to identify specific steps of the exocytotic process that are deregulated in the tumor. Uncovering why and how secretion in neuroendocrine tumors becomes uncontrolled will help to develop therapy strategies aiming to prevent hyper-secretion of the tumor, hence decreasing the associated-clinical risks as well as the tumor growth itself.  We believe that this collaboration will create a unique synergy from which will emerge a new field of investigation at the interface between medicine and cell biology.

 

Investissements d'Avenir