Mechanisms of small cell lung cancer metastasis

Abstract

Metastasis is a major cause of morbidity and mortality in cancer patients. However, the molecular and cellular mechanisms underlying the ability of cancer cells to metastasize remain relatively poorly understood. Among all solid tumors, small cell lung cancer (SCLC) has remarkable metastatic proclivity, with a majority of patients diagnosed with metastatic disease. Our understanding of SCLC metastasis has been hampered for many years by the paucity of material from primary tumors and metastases, as well as the lack of faithful pre-clinical models. Here, we review recent advances that are helping circumvent these limitations. These advances include methods that employ circulating tumor cells from the blood of SCLC patients and the development of diverse genetically engineered mouse models of metastatic SCLC. New insights into the cellular mechanisms of SCLC metastasis include observations of cell fate changes associated with increased metastatic ability. Ongoing studies on cell migration and organ tropism promise to expand our understanding of SCLC metastasis. Ultimately, a better molecular understanding of metastatic phenotypes may be translated into new therapeutic options to limit metastatic spread and treat metastatic SCLC.

Keywords: NFIB; SCLC; lung cancer; metastasis; tumor heterogeneity.

Figure 1. Metastatic ability of SCLC

Schematic representation of common metastatic sites in SCLC patients (A), genetically engineered mouse models (B), and pre‐clinical human models in mice (C). CDX, circulating tumor cell‐derived xenograft. See text for details.

Figure 2. Mechanisms of SCLC metastasis

The metastatic ability of SCLC is regulated by a number of factors, including the cell type from which tumors originate, the genetic make‐up of each tumor, interactions between cancer cells and other cells in the tumor microenvironment, and epigenetic factors regulating cell fate and intratumoral heterogeneity. See text for details.