Neuroendocrine Lung Cancer Mouse Models: An Overview

Abstract

Neuroendocrine lung tumors comprise a range of malignancies that extend from benign

tumorlets to the most prevalent and aggressive Small Cell Lung Carcinoma (SCLC). They also

include low-grade Typical Carcinoids (TC), intermediate-grade Atypical Carcinoids (AC) and highgrade Large Cell Neuroendocrine Carcinoma (LCNEC). Optimal treatment options have not been

adequately established: surgical resection when possible is the choice for AC and TC, and for SCLC

chemotherapy and very recently, immune checkpoint inhibitors. Some mouse models have been

generated based on the molecular alterations identified in genomic analyses of human tumors.

With the exception of SCLC, there is a limited availability of (preclinical) models making their

development an unmet need for the understanding of the molecular mechanisms underlying these

diseases. For SCLC, these models are crucial for translational research and novel drug testing, given

the paucity of human material from surgery. The lack of early detection systems for lung cancer point

them out as suitable frameworks for the identification of biomarkers at the initial stages of tumor

development and for testing molecular imaging methods based on somatostatin receptors. Here,

we review the relevant models reported to date, their impact on the understanding of the biology

of the tumor subtypes and their relationships, as well as the effect of the analyses of the genetic

landscape of the human tumors and molecular imaging tools in their development