ABSTRACT
Adenocarcinoma has become the most prevalent lung cancer sub-type and its frequency is increasing. The earliest stages in the development of lung adenocarcinomas are visible using modern computed tomography (CT) as ground glass nodules. These pre-invasive nodules can progress over time to become invasive lung adenocarcinomas. Lesions in this developmental pathway are termed 'adenocarcinoma spectrum' lesions. With the introduction of lung cancer screening programs there has been an increase in the detection of these lesions raising questions about natural history, surveillance and treatment. Here we review how the radiological appearance of an adenocarcinoma spectrum lesion relates to its underlying pathology and explore the natural history and factors driving lesion progression. We examine the molecular changes that occur at each stage of adenocarcinoma spectrum lesion development, including the effects of the driver mutations, EGFR and KRAS, that are key to invasive adenocarcinoma pathology. A better understanding of the development of pre-invasive disease will create treatment targets. Our understanding of how tumours interact with the immune system has led to the development of new therapeutic strategies. We review the role of the immune system in the development of adenocarcinoma spectrum lesions. With a clear preinvasive phase there is an opportunity to treat early adenocarcinoma spectrum lesions before an invasive lung cancer develops. We review current management including surveillance, surgical resection and oncological therapy as well as exploring potential future treatment avenues.
Subject(s)
Adenocarcinoma of Lung/diagnosis , Adenocarcinoma of Lung/therapy , Lung Neoplasms/diagnosis , Lung Neoplasms/therapy , Adenocarcinoma of Lung/diagnostic imaging , Adenocarcinoma of Lung/pathology , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Neoplasm Invasiveness , Tomography, X-Ray ComputedSubject(s)
Carcinoid Tumor/diagnosis , Gallium Radioisotopes , Lung Neoplasms/diagnosis , Magnetic Resonance Imaging/methods , Multimodal Imaging/methods , Organometallic Compounds , Positron-Emission Tomography/methods , Radiopharmaceuticals , Humans , Male , Middle Aged , Octreotide/analogs & derivativesABSTRACT
Lung cancer is the biggest cancer killer in the UK and despite recent therapeutic advances there is a desperate need for new therapies to improve outcomes from this devastating disease. Through defining the spatial location of the airway epithelial stem or progenitor cell populations and their mechanisms of maintenance and repair of the epithelium it is becoming clear that these populations are situated at areas corresponding to those involved in lung cancer initiation. We explore the evidence for stem cells being the cancer initiator cell and for a 'lung cancer stem cell' within tumours that may be the cause of resistance to current therapies.
