A review of novel biological tools used in screening for the early detection of lung cancer

Abstract

Lung cancer is the most common cancer worldwide and causes more deaths per year than any other cancer. It has a very poor 5-year survival rate of 8-16%, partly because of comorbidity preventing curative treatments but mainly because of the disease presenting with symptoms only when it is at an advanced and incurable stage. When lung cancer is detected earlier and is amenable to radical treatments such as potentially curative surgery and radical radiotherapy, 5-year survival rates are much higher (up to 67%). Therefore reliable detection of lung cancer at this earlier (usually asymptomatic) stage of disease should be an important way to improve outcomes. This review discusses the principles of screening with respect to lung cancer, concentrating mainly on the biological modalities used to detect it. The lack of impact achieved by early studies using sputum cytology (in conjunction with chest radiographs) is described, and then newer technology used to measure other biomarkers in sputum, serum, exhaled breath and bronchial mucosa to diagnose (early) lung cancer is detailed. Many techniques show promise, but debate continues about which population to screen and what is the most (cost) effective modality to use. Moreover, no single biomarker or combination of biomarkers in screening has yet been shown to reduce lung cancer mortality in large prospective randomised studies.Lung cancer is the most common cancer worldwide in terms of both incidence and mortality, with 1.3 million new cases being diagnosed each year and 1.2 million deaths, with Europe and North America having the highest incidence and prevalence rates.1 2 Compared with other common cancers such as prostate and breast cancer, lung cancer has much lower survival rates, and, despite advances in radiological tests, particularly CT and positron emission tomography scanning, surgical techniques and postoperative management, radiotherapy delivery and new chemotherapeutic agents, the long-term survival from lung cancer has remained remarkably constant and has not improved significantly over the last 20 years.3 Apart from lowering its incidence by reducing cigarette smoking, the key to improving lung cancer survival at present is to diagnose it at an earlier stage. This has led to decades of research to identify a suitable screening technique in order to reduce mortality.The objectives of this article are to describe the principles of screening and show how they are relevant to lung cancer. We will briefly discuss purely radiological attempts at screening with lowdose spiral CT (LDCT) and how simple radiology (chest radiographs (CXRs)) has been combined with sputum cytology, before describing in more detail how novel biological techniques (or biomarkers) have been tried and are still being applied in the detection of lung cancer. We will also explain some of the biological reasoning for the use of certain biomarkers and, in particular, how they are based on a better molecular understanding of lung carcinogenesis.

Identification of a new microRNA expression profile as a potential cancer screening tool

“…One recent review states: "Overall, no single cheap and reliable test has yet been identified for the effective screening of lung cancer in large population studies, but work is in progress." 5 Effective and financially feasible screening for patients at a high risk of developing lung cancer is, therefore, a high research priority.…”

Diagnosis of Lung Cancer — Improving Survival Rates

“…Biological tools, such as testing serum for tumour-associated antibodies, detection of gene-promoter hypermethylation in sputum samples, exhaled breath volatile organic compounds and detection of novel proteins in serum or sputum are also in development 31 . Unfortunately, none of these is currently ready for use in clinical practice.…”

Kaempferol modulates the metastasis of human non-small cell lung cancer cells by inhibiting epithelial-mesenchymal transition

“…It can be categorized into two sub-types: nonsmall cell lung cancer (Koh et al, 2012) and small cell lung cancer. Despite many efforts to improve lung cancer outcome, long-term survival has not improved significantly over the last 20 years, with a 5-year cumulative survival rate that remains very dismal at only 15% (Ghosal et al, 2009). Current standard therapies limited to chemotherapy and radiotherapy or both rarely cure this disease, thus accentuating the need for more effective and alternate therapeutic strategies.…”