Precision medicine in gastroenteropancreatic neuroendocrine neoplasms: Where are we in 2023?

Risk factors, prognostic factors, and nomograms for distant metastases in patients with gastroenteropancreatic neuroendocrine tumors: a population-based study

“…Currently, the treatment of patients with advanced GEP-NETs faces many problems. The precision therapeutic methods of molecular targeting have achieved remarkable results in the field of oncology, but the therapeutic application in GEP-NENs is still immature, and some targets are controversial ( 20 ). Peptide receptor radionuclide therapy-based combination therapies with and anti-vascular endothelial growth factor drugs with standard chemotherapy have achieved good results, but still need to be studied in larger trials ( 21 ).…”

Molecular Classification of Gastrointestinal and Pancreatic Neuroendocrine Neoplasms: Are We Ready for That?

“…Most of the molecular studies available on digestive NET have been performed on pancreatic NET (PanNET), from which we have learned important general lessons on NEN, that are guiding actual therapeutic approaches with biological drugs [ 72 ]. The introduction, in the clinical practice, of drugs targeting, for example, somatostatin receptors (both in the form of medical and peptide related radio-nuclide therapy), mTOR/PI3K/AKT pathway, MGMT, and hypoxia-related mechanisms have reoutlined the approach to advanced NET and have given new chances to the patients, and also the impact on diagnostic procedures (functional imaging) cannot be underestimated [ 73 , 74 ].…”

“…Although it may seem obvious, the most important parameter on which therapy is currently based is the distinction between NEC and NET. In fact, the former are treated with platinum-based chemotherapy combined with etoposide, inspired by the similarity to their pulmonary counterpart [ 134 , 135 ], whereas NET are basically resistant to chemotherapy schedules used for epithelial malignancies commonly seen in the digestive tract (i.e., adenocarcinoma) [ 72 ]. This different response to traditional anti-neoplastic drugs is easily understandable in the light of the very high proliferation rate of NEC, compared to the distinctively low proliferation rate of NET.…”

“…However, this is everyday experience of clinical practice; NEC invariably recur in a short time despite the initial response to chemotherapy and eventually kill the patient [ 134 ]. On the other hand, despite the well differentiated morphology, the low proliferation index, and the claimed “indolent” behavior of NET, a significant proportion of patients experience advanced disease at diagnosis or metachronous metastases and need to be treated with medical therapy [ 72 ]. From here, the need to find new and effective therapeutic strategies arises, and the molecular-based therapeutic approach opens new perspectives in this sense.…”

Neuroendocrine Neoplasia: From Pathophysiology to Novel Therapeutic Approaches

“…The domain of NENs involves both adult and (rarely) paediatric patients; heterogeneous NENs with hereditary components or sporadic types of them, as well as NENs with different prevalence ratios from various studies, are more frequently being identified as gastro-entero-pancreatic (GEP) and lung NENs [5]. Despite NENs remaining a rather uncommon finding in the general population (currently the incidence rate is 6 per 100,000 people and the prevalence is 35 per 100,000 people), an increasing incidence of 6.4 times has been reported over the last 40 years [6][7][8].…”