Applying the Use of Novel Biomarkers for Neuroendocrine Tumors in the Clinic: Where are We Now?

Abstract

Chromogranin A (CgA) is a general marker for NETs, which can also be found elevated in various inflammatory conditions, such as inflammatory bowel disease and rheumatoid arthritis, as well as essential hypertension, chronic heart failure, impaired renal function, pregnancy, steroid treatment or glucocorticoid excess, liver disease, hyperparathyroidism, chronic atrophic gastritis and finally treatment with proton-pump inhibitors (PPI) (1 ,2). [...]CgA is elevated in other non-neuroendocrine neoplastic tumors, such as pancreatic adenocarcinoma, prostate carcinoma and small-cell lung carcinoma. Additionally, there is a lack of standardization of concentrations between different laboratories and even within commercial tests for CgA and other monoanalyte biomarkers, so that the results may exhibit wide variations being difficult to interpret (2). [...]CgA is a nonspecific (10-35% specificity) and moderately sensitive marker (60-90% sensitivity) (2). Regarding other targeted novel therapies, IL-8, sVEGFR-3 and SDF-1α were recently identified as predictors of response to tyrosine kinase inhibitor sunitinib in a Phase II study (19). [...]O6-methylguanidine-DNA methyltransferase expression is currently evaluated as a predictor of response to temozolomide treatment. The gene transcript PCR analysis is standardized and not affected by PPI and different types of food. [...]it has demonstrated promising results regarding its ability to provide therapeutically relevant information in terms of monitoring disease progression and treatment response, with the latter being the best added value of this test compared with monoanalytes.