Lung cancer is the leading cause of cancer-related death in the world. It is broadly divided into small cell (SCLC, approx. 15% cases) and non-small cell lung cancer (NSCLC, approx. 85% cases). The main histological subtypes of NSCLC are adenocarcinoma and squamous cell carcinoma, with the presence of specific DNA mutations allowing further molecular stratification. If identified at an early stage, surgical resection of NSCLC offers a favourable prognosis, with published case series reporting 5-year survival rates of up to 70% for small, localized tumours (stage I). However, most patients (approx. 75%) have advanced disease at the time of diagnosis (stage III/IV) and despite significant developments in the oncological management of late stage lung cancer over recent years, survival remains poor. In 2014, the UK Office for National Statistics reported that patients diagnosed with distant metastatic disease (stage IV) had a 1-year survival rate of just 15–19% compared with 81–85% for stage I.

https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.170070

Progress and prospects of early detection in lung cancer

Biomarkers in Lung Cancer Screening: Achievements, Promises, and Challenges

The role of mucus on drug transport and its potential to affect therapeutic outcomes

Several discoveries have paved the way to personalise cancer medicine and a tremendous gain of knowledge in genomics and molecular mechanisms of cancer progression cumulated over the last years. Big stories in biology commonly start in a simple model system. No wonder microRNAs have been identified as regulators of embryonic development in the nematode Caenorhabditis elegans. From the first identification in worms to the first-in-man microRNA-based clinical trial in humans, almost 20 years passed. In this review we follow the story of understanding microRNA alterations in cancer, describe recent developments in the microRNA field and critically discuss their potential as diagnostic, prognostic and therapeutics factors in cancer medicine. We will explain the rationale behind the use of microRNAs in cancer diagnosis and prognosis prediction, but also discuss the limitations and pitfalls associated with this. Novel developments of combined microRNA/siRNA pharmacological approaches will be discussed and most recently data about MXR34, the first-tested microRNA drug will be described.

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MicroRNAs in cancer: from developmental genes in worms to their clinical application in patients

Lung cancer is the leading cause of cancer mortality worldwide. microRNAs (miRNAs) have been established as players with a relevant role in lung cancer development, epithelial-mesenchymal transition and response to therapy. Additionally, in the last decade, miRNAs, measured in resected tumor samples or in fine-needle aspirate samples have emerged as compelling biomarkers for tumor diagnosis, prognosis, and prediction of response to treatment, due to the ease of their detection and in their extreme specificity. Moreover, miRNAs present in sputum, in plasma, in serum or in whole-blood have increasingly been explored in the last 5 years as less invasive biomarkers for the early detection of cancers.

microRNA and Lung Cancer.

Purpose: The early detection of lung cancer in heavy smokers by low-dose CT (LDCT) can reduce the mortality. However, LDCT screening increases the number of indeterminate solitary pulmonary nodules (SPN) in asymptomatic individuals, leading to overdiagnosis. Making a definitive preoperative diagnosis of malignant SPNs has been a clinical challenge. We have demonstrated that sputum miRNAs could provide potential biomarkers for lung cancer. Here, we aimed to develop sputum miRNA biomarkers for diagnosis of malignant SPNs. Experimental Design: Using quantitative RT-PCR, we evaluated expressions of 13 sputum miRNAs, previously identified sputum miRNA signatures of lung cancer, in a training set of 122 patients with either malignant ( n = 60) or benign SPNs ( n = 62) to define a panel of biomarkers. We then validated the biomarker panel in an internal testing set of 136 patients with either malignant ( n = 67) or benign SPNs ( n = 69), and an external testing cohort of 155 patients with either malignant ( n = 76) or benign SPNs ( n = 79). Results: In the training set, a panel of three miRNA biomarkers (miRs21, 31, and 210) was developed, producing 82.93% sensitivity and 87.84% specificity for identifying malignant SPNs. The sensitivity and specificity of the biomarkers in the two independent testing cohorts were 82.09% and 88.41%, 80.52% and 86.08%, respectively, confirming the diagnostic value. Conclusions: Sputum miRNA biomarkers may improve LDCT screening for lung cancer in heavy smokers by preoperatively diagnosing malignant SPNs. Nevertheless, a prospective study in a large population to validate the biomarkers is needed. Clin Cancer Res; 21(2); 484–9. ©2015 AACR .

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Rixin Zhou

Papers

Sputum microRNA biomarkers for identifying lung cancer in indeterminate solitary pulmonary nodules.