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**165**

**1. Introduction**

**Chapter 10**

Lung Cancer

multidisciplinary management of lung cancer.

and cancer metastasis remains to be further elucidated [1].

**Keywords:** CTC, CTEC, ctDNA, therapeutic resistance, aneuploidy, iFISH

Recent progress in multidisciplinary management of advanced lung cancer has triggered enthusiasm in investigating both prognostic roles of tumor microenvironment (TME) and clinical utilities of liquid biopsy in lung cancer patients [1, 2]. How the tumor-reprogrammed lung TME promotes primary tumor progression

Aberrant stromal and infiltrated immune cells, sustained neovascularization, as well as dysfunctional neoangiogenic vasculatures in solid tumors all contribute

*Peter Ping Lin*

**Abstract**

Liquid Biopsy Analysis of

Circulating Tumor Biomarkers in

Risk stratification, prognostication and longitudinal monitoring of therapeutic

efficacy in lung cancer patients remains highly challenging. It is imperative to establish robust surrogate biomarkers for identifying eligible patients, predicting and effectively monitoring clinical response as well as timely detecting emerging resistance to therapeutic regimens. Circulating tumor biomarkers, analyzed by liquid biopsy, are primarily composed of nucleic acid-based circulating tumor DNA (ctDNA) and an aneuploid cell-based category of circulating tumor cells (CTCs) and circulating tumor-derived endothelial cells (CTECs). Unlike ctDNA, cancer cells are the origin of all categories of various tumor biomarkers. Involvement of aneuploid CTCs and CTECs in tumorigenesis, neoangiogenesis, tumor progression, cancer metastasis and post-therapeutic recurrence has been substantially investigated. Both CTCs and CTECs possessing an active interplay and crosstalk constitute a unique category of cellular circulating tumor biomarkers. These cells concurrently harbor the intact cancer-related genetic signatures and full tumor marker expression profiles in sync with disease progression and therapeutic process. Recent progress in clinical implementation of non-invasive liquid biopsy has made it feasible to frequently carry out ctDNA analysis and unbiased detection of a full spectrum of non-hematologic circulating rare cells including CTCs and CTECs in lung cancer patients, regardless of variation in heterogeneous cell size and cancer cell surface anchor protein expression. *In situ* phenotypic and karyotypic comprehensive characterization of aneuploid CTCs and CTECs, in combination with single cell-based genotyping and improved ctDNA analyses, will facilitate and benefit

## **Chapter 10**
