TITLE:
Pre-malignant processes of smoking-induced lung adenocarcinoma development: A conceptual biological model
AUTHORS:
Frank Tobin, Gregory Vuillaume, Marja Talikka, Gaelle Diserens, Gaelle Diserens, Manuel C. Peitsch, Julia Hoeng
KEYWORDS:
Lung Adenocarcinoma; Cigarette Smoke; Field Cancerization
JOURNAL NAME:
Advances in Lung Cancer,
Vol.2 No.2,
June
25,
2013
ABSTRACT: Chronic exposure to
cigarette smoke is the leading cause of human lung cancer and its most
prevalent form, adenocarcinoma. However, the mechanisms by which smoking
induces adenocarcinoma are largely inferred from the analysis of fully
developed tumors. The current work focuses on the early events that precede the
existence of clinically detectable tumors and where the progressive mechanisms
are believed to be different from the ones driving established tumor growth. Biological
information was drawn from the literature and generalized into a conceptual
model, or framework, which describes and integrates the main processes involved
in the early stages of smoking-induced lung adenocarcinoma development. No such integrative representation currently exists. The
biological framework presented here is based on the “field of injury” of the
lung. It covers the smoking-induced stepwise transition of unexposed (naive)
lung tissue to the first appearance of neoplastic cells through defined tissue
states referred to as pre-field and field. Each tissue state exhibits its own
formalized characteristics (or phenotype properties), which evolve as a result
of the combined effects of smoking, the interactions between the different
tissue properties, and the local environment represented in the framework as
lung inflammation and immune surveillance. The resulting network of influences
between the lung tissue states and properties provides a good understanding of
the early events involved in lung adenocarcinoma triggered by smoking. The
resulting conceptual model—an integrative mechanistic
hypothesis—can explain a broad range of cigarette smoking and smoking cessation
scenarios.