Evolution of Neuroendocrine Tumor Therapy

Abstract

To better understand developments in treatment of neuroendocrine tumors of the gastroenteropancreatic system, and the pivotal roles of native somatostatin and its long-acting analogues play in normal peptide regulation and neuropeptide excess associated with neuroendocrine tumors (NETs), this article delineates and defines distinct eras in the history and discovery of gastrointestinal endocrinology. We highlight the collaboration between academia and industry in basic science and the clinical research that advanced Lu-177-DOTATATE to approval as standard of care therapy for low-grade NETs. Examples of new radioisotopes and therapy compounds currently in development for diagnosis and therapy for high-grade NETs are also discussed.

Keywords: GI Hormones; Gastroenteropancreatic; Neuroendocrine tumor; Octreotide; PRRT; Therapy.

Fig. 1.

Peptides identified in the mammalian gastroenteropancreatic system. ^a Somatostatin has all regulatory actions: endocrine, paracrine, neuroendocrine, autocrine. ^b RIA (radioim-munoassay) first described in 1959.^,

Fig. 2.

Carcinoid and neuroendocrine tumors: cancer management and treatment options of care. ^a Most recently FDA approved. FDG, fluorodeoxyglucose; WHO, World Health Organization. (Courtesy of Iowa NET Team, Iowa City, IA.)

Fig. 3.

Somatostatin and its congeners.

Fig. 4.

A timeline of octreotide culminating in development of PRRT and theranostics.

Fig. 5.

Targeted molecular imaging and therapy (PRRT) and theranostics concept. Theranostics is the use of diagnostic radionuclides (⁶⁸Cu, ⁶⁸Ga) and therapeutic radionuclides (⁹⁰Y, ¹⁷⁷Lu, ²¹²Pb) labeled to the same somatostatin congener (TOC or TATE). (Courtesy of H. Maecke, University Hospital, Basel, CH.)