A Critical View of Molecularly Target Therapy for Digestive Endocrine Tumours

Abstract

Enteropancreatic endocrine tumours (EP ETs) are relatively rare neoplasms constituting a heterogeneous nosological category. Most EP ETs present with metastatic disease, are well-differentiated and have a relatively slow growth-rate, with high percentage of stable disease and relative long survival. In those patients with progressive disease biotherapy and chemotherapy have relatively low response rates. In this context, novel therapies are needed, especially for the treatment of progressive, metastatic disease which represents, in this field, the main therapeutic challenge. EP ETs seem an appropriate model for targeting angiogenesis, with solid data from animal and in vitro models. Effects of angiogenesis inhibitors, such as bevacizumab, sunitinib, thalidomide and endostatin seem promising especially in patients with pancreatic tumours. Targeting other tyrosine kinases such as EGFR (with gefitinib) or c-KIT (imatinib) has also been tested, with various degree of response. The mTOR pathway also looks as an interesting pathway to be targeted, with interesting data in some clinical trials. The main limits of the available data are represented by the high heterogeneity of patients and of inclusion criteria. Moreover, few studies included patients with documented progressive disease before treatment, thus making difficult to understand the real efficacy of treatment on spontaneous tumour growth. Future studies should evaluate combination therapies in more homogeneous populations of patients, and include clear definition of the individual progression rate before and after the study entry. An informative review of novel patents and therapeutic targets of enteropancreatic endocrine tumours are also discussed. Keywords: Gastroenteropancreatic endocrine tumours, carcinoids, novel therapeutic targets, angiogenesis, tyrosine kinase inhibitors, small molecules, VEGF, c-KIT, PDGFR, mTOR