*DANIEL CHELSKY

Blood-based biomarkers to diagnose neuroendocrine tumors, follow disease progression and identify new therapeutic targets

Challenge: Cancer remains a leading cause of death in the developed world. Endocrine tumors derived from hormone-producing cells are particularly problematic. This type of tumor can over-produce hormones, which can induce serious complications. Early and accurate diagnosis is currently very difficult, and treatments of late-stage tumors are ineffective. There is, therefore, an urgent need to improve diagnosis and develop more effective therapies against neuroendocrine tumors.

Solution: Because the aggressiveness of neuroendocrine tumours appears related to their level of secretion, the researchers concentrated their efforts on secreted protein biomarkers. The team used Caprion’s large scale proteomics approach on both neuroendocrine cancer cell lines and tumour-derived tissues. Over 350 differentially expressed proteins were selected as candidate diagnostic biomarkers. The researchers then assessed their presence in sera from subjects with pheochromocytomas (a tumor developing in the adrenal gland) or healthy controls using a targeted and quantitative “multiple reaction monitoring” mass spectrometry (MRM-MS) assay. Further prioritization resulted in the selection of 9 candidate targets involved in cell proliferation and tumor growth, membrane fusion, membrane trafficking or modulation of Rho GTPase activities. In vitro silencing of many of these proteins significantly inhibited secretion suggesting that they represent novel and attractive targets to modulate secretion in neuroendocrine cells.

Achievements/Impact: The panel of blood-based protein biomarkers identified in this project could lead to a better diagnosis of neuroendocrine cancer and to improved monitoring of disease progression. Some of these markers could even represent new therapeutic targets. Building on these results, a partnership has been established between Caprion, the Centre national de la recherche scientifique (CNRS, France) and Firalis. The French biotech has licensed some biomarkers and intend to develop immunoassays for an eventual commercialization.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Principal Investigator:

Daniel Chelsky
Caprion Biosciences

Stéphane Gasman
CNRS (France)

Co-investigators

Eustache Paramithiotis
Caprion Biosciences

Completed Project
$ 1,158,000 / 3 years
Supported by CQDM through:
• AstraZeneca
• Merck
• Pfizer
• BL-NCE
 
And by a co-funding partner:
• Alsace Biovalley (France)
• Caprion Biosciences