Clinical and Preclinical Advances in Gastroenteropancreatic Neuroendocrine Tumor Therapy

Abstract

The molecular events leading to gastroenteropancreatic neuroendocrine tumor (GEP-NET) formation are largely unknown. Over the past decades, systemic chemotherapies have been replaced by therapies directed at particular molecular targets such as the somatostatin receptors, mTOR complexes or proangiogenic molecules. These approaches have demonstrated some success in subtypes of this heterogeneous tumor group, but responses are still widely varied. This review highlights the clinical trials ongoing for neuroendocrine tumors (NETs) and includes emerging immunotherapy, which holds great promise for NETs based on successes in other tumor types. Current avenues of preclinical research, including Notch and PI3K/AKT, will lead to additional targeted therapies based on genome-wide studies that have cast a wide net in the search for driver mutations. Future preclinical and clinical investigations are required to identify those mutations predictive of therapeutic response or disease progression. Results of current clinical trials outlined here will better inform patient management with respect to agent selection, timing, duration and combination therapy in the treatment of NETs.

Management of Typical and Atypical Pulmonary Carcinoids Based on Different Established Guidelines

“…Given the advancements with novel therapies such as PRRT, it is time to test if this therapy can be combined with other established therapies in the field of NETs. There are ongoing trials where PRRT is being combined with capecitabine for GEP NET patients, and another trial where PRRT is being combined with capecitabine and temozolomide in midgut and pancreatic NET patients [101].…”

Clinical presentation and management of primary ovarian neuroendocrine tumor in multiple endocrine neoplasia type 1

“…Another randomized trial comparing lanreotide with placebo in 88 patients demonstrated that lanreotide was associated with significantly higher rates of PFS at 24 months – 65.1% (95% CI, 54.0–74.1) compared to 33.0% (95% CI, 23.0–43.3) in the placebo group ( P < 0.001) (13). In addition to control of tumor growth, SSAs have been shown to highly effective in controlling symptoms of hormone oversecretion in over half of patients (14). Our patient is currently receiving LAR octreotide as an adjunct after surgery for the residual disease.…”

“…Therapies targeting VEGF (sunitinib, pazopanib, cabozantinib and axitinib) and mTOR (everolimus) have been used with promising results in NETs originating from other sites of the body (primarily gastrointestinal NETs and pancreatic NETs). Sunitinib was FDA approved for advanced pancreatic NETs after a phase III study showed PFS advantage compared to placebo (14). A summary of clinical studies with targeted agents in the treatment of advanced NETs is provided in Table 1.…”

Nivolumab-induced autoimmune diabetes mellitus and hypothyroidism in a patient with rectal neuroendocrine tumor

“…There have been important advancements in cancer therapy over the past few years, especially in the area of neuroendocrine tumors. Systemic chemotherapy is beginning to be replaced by therapeutics specifically targeted at molecular entities, which is having an impact on agent selection, patient management, and long-term outcomes [1].…”