What molecular alterations causes NETs to develop and grow?

This really important piece of work looks at the the landscape of molecular alterations in pancreatic NETs and NETs of the small intestine.

We know that Neuroendocrine Neoplasms are heterogenous and they they display a huge variability and behaviour. Some behave indolently and some aggressively, and some in-between. The incidence  ( amount of people diagnosed) has more than tripled in the last 40 years and of course we know that the prevalence ( number of people ‘living with’) is really high compared to other cancers such as pancreatic cancer.

Most of the tumours present with non-specific symptoms, or no symptoms at all. This is something not often understood as people assume all NENs release hormones that induce a clinical syndrome. 

In the Neuroendocrine Carcinoma (NEC) group, There are 2 main genes that are seen as the ‘drivers’ that cause gene mutations and inactivation of TP53 and RB1 genes. Other Neuroendocrine Tumours lack these alterations. 

There is also a biological difference that we know about from the grading and KI67 counts: Below is a great visual from the NET Research Foundation in America, that I think makes things very clear! 

The paper goes on to blind us with science and the details of genomics, epigenomics and transcriptomics, but it does conclude that that pancreatic and small intensional neoplasms display different relationships with genetic or hormone related syndromes, display different driver alterations, have a different amount of aggressive cases and often have a wide spectrum of outcomes. 

This all means that we need to have multiple markers available to ensure that any given targeted drug will work on a given patient for the most effective outcomes. 

Work is continuing across the spectrum to identify the drivers that cause progression and find the right targeted therapy to alter that path.

The Landscape of molecular alterations in pancreatic and small intestinal neuroendocrine tumours
Aldo Scarpa
Annales d’Endocrinologie 80 (2019) 153-158
 
Click to enlarge image