Lung NETs and GEPNETs: One Cancer with Different Origins or Two Distinct Cancers?

Simple Summary This review examined the disparities between lung neuroendocrine tumors and gastroentero-pancreatic neuroendocrine tumors, two types of neuroendocrine tumors that originate from different parts of the body and have historically been treated similarly. This research delves into the differences in genetic makeup, behavior, and response to treatments such as chemotherapy, immunotherapy, and targeted therapies between these two types of tumors. This study aimed to explore these distinctions to develop more personalized and effective treatment strategies for patients with lung and gastroenteropancreatic neuroendocrine tumors. By recognizing and treating these two types of cancer as distinct entities rather than as a single disease, the medical community can significantly improve patient outcomes and highlight the importance of this research.Abstract Lung neuroendocrine tumors (LNETs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are two distinct types of neuroendocrine tumors (NETs) that have traditionally been treated as a single entity despite originating from different sources. Although they share certain phenotypic characteristics and the expression of neuroendocrine markers, they exhibit differences in their microenvironment, molecular mutations, and responses to various therapeutic regimens. Recent research has explored the genetic alterations in these tumors, revealing dissimilarities in the frequently mutated genes, the role of EGFR in carcinogenesis, the presence of transcription factors, and the immunogenicity of the tumor and its microenvironment. Spread Through Air Spaces (STAS), a phenomenon unique to lung carcinomas, appears to play a crucial role in LNET prognosis. These distinctions are also evident in the cascade response of lung and GI tract neuroendocrine tumors to somatostatin analogs, Peptide Receptor Radionuclide Therapy (PRRT), chemotherapy, and immunotherapy. Identifying similarities and differences between the two groups may improve our understanding of the underlying mechanisms and facilitate the development of more effective treatment strategies.