Mechanisms and Future of Non-Small Cell Lung Cancer Metastasis.

Lung cancer, renowned for its fast progression and metastatic potency, is rising to become a leading cause of death globally. It has been long observed that lung cancer is particularly ept in spawning distant metastasis at its early stages, and it can readily colonize virtually any human organ. In recent years, cancer research has shed light on why lung cancer is endowed with its exceptional ability to metastasize. In this review, we will take a comprehensive look at the current research on lung cancer metastasis, including molecular pathways, anatomical features and genetic traits that make lung cancer intrinsically metastatic, as we go from lung cancer's general metastatic potential to the particular metastasis mechanisms in multiple organs. We highly concerned about the advanced discovery and development of lung cancer metastasis, indicating the importance of lung cancer specific gene mutations, heterogeneity or biomarker discovery, and discussing potential opportunities and challenges. We will also introduce some current treatments that targets certain metastatic strategies of non-small cell lung cancer (NSCLC). Advances made in these regards could be critical to our current knowledge base of lung cancer metastasis.

Critical steps to tumor metastasis: alterations of tumor microenvironment and extracellular matrix in the formation of pre-metastatic and metastatic niche.

For decades, cancer metastasis has been a heated topic for its high mortality. Previous research has shown that pre-metastatic niche and metastatic niche are the 2 crucial steps in cancer metastasis, assisting cancerous cells' infiltration, survival, and colonization at target sites. More recent studies have unraveled details about the specific mechanisms related to the modification of pro-invasion environments. Here, we will review literatures on extracellular matrix (ECM) alterations, general cancer metastasis, organ specificity, pre-metastatic niche, metastatic niche, colony formation and impact on the course of metastasis. Respectively, the metastatic mechanisms like effect of hypoxia or inflammation on pre-metastatic niche construction, as well as the interaction between cancer cells and local milieu will be discussed. Based on the evidences of metastatic niches, we revisit and discussed the "Seed and Soil" hypothesis by Paget. This review will seek to provide insight into the mechanism of metastatic organ specificity which pre-metastatic niche and metastatic niche might suggest from an evolutionary aspect.