Lung cancer chemoprevention: current status and future prospects

Abstract

Lung cancer is the leading cause of cancer death worldwide, making it an attractive disease for chemoprevention. Although avoidance of tobacco use and smoking cessation will have the greatest impact on lung cancer development, chemoprevention could prove to be very effective, particularly in former smokers. Chemoprevention is the use of agents to reverse or inhibit carcinogenesis and has been successfully applied to other common malignancies. Despite prior studies in lung cancer chemoprevention failing to identify effective agents, we now have the ability to identify high-risk populations, and our understanding of lung tumour and premalignant biology continues to advance. There are distinct histological lesions that can be reproducibly graded as precursors of non-small-cell lung cancer and similar precursor lesions exist for adenocarcinoma. These premalignant lesions are being targeted by chemopreventive agents in current trials and will continue to be studied in the future. In addition, biomarkers that predict risk and response to targeted agents are being investigated and validated. In this Review, we discuss the principles of chemoprevention, data from preclinical models, completed clinical trials and observational studies, and describe new treatments for novel targeted pathways and future chemopreventive efforts.

Early Events in the Molecular Pathogenesis of Lung Cancer

“…Additionally, early discovery and diagnosis of lung cancers is still suboptimal (5). These limitations are largely attributed to the scarcity of reliable molecular targets (e.g., genomic loci or genes) on which to assess the efficacy of agents in clinical trials (6,16,17) and markers for early detection of lesions (5,18). Identification of these markers and targets is thought to heavily rest on comprehending early lung oncogenesis.…”

“…However, and to date, large-scale lung cancer chemoprevention trials have been negative with neutral, or even harmful, results (6,17). Additionally, early discovery and diagnosis of lung cancers is still suboptimal (5).…”

“…The 5-year survival rates for advanced late-stage lung cancer remain poor (5%; refs. 3,4), leading to the supposition that early diagnosis of lung cancer or its treatment in premalignant stages will reduce the public health burden of this fatal malignancy (5)(6)(7)(8). The vast majority (85%) of lung cancers are causally linked to tobacco carcinogen exposure (3,4).…”

Chemokines and their receptors in lung cancer progression and metastasis

“…Fortunately, early detection with a lung cancer screening program using low-dose computed tomography (LDCT) scans has recently brought bright prospects, and the mortality rate has reduced by 20% (National Lung Screening Trial Research, 2011). Nevertheless, overall, 5-yearsurvival remains low, at less than 20% (Keith and Miller, 2013). Therefore, early detection is only the first step; personalized precise treatments following detection, based on molecular mechanisms, are also crucial; these treatments either fight tumor cells directly or modify the tumor microenvironment indirectly (Burger and Gribben, 2014).…”

Two Molecular Markers of Early Non-Small Cell Lung Carcinoma Based on Gene Expression in Peripheral Blood

“…Lung cancer is among the most common cancers worldwide and over 80% of the lung cancer patients have an approximately 5-year survival rate after diagnosis [1]. Lung cancer is categorized into two types of NSCLC and small cell lung cancer (SCLC).…”