Advances and Possible Personalized Medicine in Patients With Gastroenteropancreatic Neuroendocrine Neoplasia

Doctor consulting patient in clinic
Doctor consulting patient in clinic
Investigators reviewed recent advances GEPNEN research and discussed the challenges and advances still needed to provide patients personalized medicine.

Has the diagnosis and treatment for gastroenteropancreatic neuroendocrine neoplasia (GEPNEN) progressed to the point in which personalized medicine is now available? The authors of a review of recent advances for GEPNEN, published in Gut, discussed the challenges and advances still needed before personalized medicine may be offered to patients.

Neuroendocrine neoplasia (NEN) is a rare epithelial cancer which has been rising in incidence globally. NEN is ubiquitous across the body with around half of the tumors occurring in the gastroenteropancreatic tissues.

To try and improve diagnosis of GEPNEN, there have been several trials incorporating newer technologies, including microRNA, messenger RNA (mRNA), and quantification of circulating tumor cells. Currently, microRNA assays cannot be recommended, as there remains a lack of power to sufficiently test its effectiveness. The diagnosis and quantification of circulating tumor cells is associated with poor prognosis and inconsistent results.

Successful diagnostic advances include the assessment of a panel of 51 neuroendocrine tumor (NET)-specific genes by means of mRNA analysis of NENs. Current studies have indicated this approach has a >95% sensitivity and specificity. Another approach, with >90% accuracy, is the analysis of 8 NET-specific growth factors and metabolomic genes from liquid biopsy samples.

The current front-line treatment for GEPNENs is somatostatin analogues (SSAs). Interferon a has been a treatment option for decades and can still be recommended for patients with somatostatin receptor (SSTR)-negative NENs or as a combinatorial therapy among patients with refractory carcinoid disease. Patients who have small intestinal or pancreatic NENs may be treated with more traditional chemotherapy, as these cancer types are chemo sensitive.

Checkpoint inhibitor therapies, which have been found to be efficacious for the treatment of many advanced malignancies have overall been observed to have little benefit among most patients with NETs. Combinatorial therapies have also shown little efficacy among patients with NETs or NENs.

The use of genomic science in research of GEPNEN has allowed for more precise diagnosis and treatment options for patients. Despite recent advances, however, the authors of this review stated that there has been slow translation of newer technologies into clinical practice.

A reason for slow progress is likely due in part to the rarity of this disease, making sufficiently powered studies difficult to carry out. GEPNEN is a highly heterogenous disease, which on the one hand lends itself to benefit from personalized medicine techniques, but on the other hand makes it difficult to study patient subtypes or obtain accurate animal models.

The review authors concluded that a ‘one-size-fits-all’ approach for the diagnosis and treatment of GEPNEN has little logical sense given the varied presentations between patients, and within patients across tumor types/tissue locations. Instead, patients should be monitored in real-time via liquid biopsy molecular assays, such that patient-specific optimization of treatment may be possible.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Rinke A, Auernhammer C J, Bodei L, et al. Treatment of advanced gastroenteropancreatic neuroendocrine neoplasia, are we on the way to personalised medicine? Gut. Published online March 10, 2021. doi: 10.1136/gutjnl-2020-321300