title: Molecular histology of lung cancer: from targets to treatments.
abstract: Lung cancer is the leading cause of cancer-related death worldwide with a 5-year survival rate of less than 15%, despite significant advances in both diagnostic and therapeutic approaches. Combined genomic and transcriptomic sequencing studies have identified numerous genetic driver mutations that are responsible for the development of lung cancer. In addition, molecular profiling studies identify gene products and their mutations which predict tumour responses to targeted therapies such as protein tyrosine kinase inhibitors and also can offer explanation for drug resistance mechanisms. The profiling of circulating micro-RNAs has also provided an ability to discriminate patients in terms of prognosis/diagnosis and high-throughput DNA sequencing strategies are beginning to elucidate cell signalling pathway mutations associated with oncogenesis, including potential stem cell associated pathways, offering the promise that future therapies may target this sub-population, preventing disease relapse post treatment and improving patient survival. This review provides an assessment of molecular profiling within lung cancer concerning molecular mechanisms, treatment options and disease-progression. Current areas of development within lung cancer profiling are discussed (i.e. profiling of circulating tumour cells) and future challenges for lung cancer treatment addressed such as detection of micro-metastases and cancer stem cells.
authors.affiliation: Faculty Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Wolfson Molecular Imaging Centre, Manchester M20 3LJ, UK. Electronic address: steven.wood@manchester.ac.uk.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Wood
authors.affiliation: Faculty Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Wolfson Molecular Imaging Centre, Manchester M20 3LJ, UK; Karolinska Institutet, Department of Oncology and Pathology, SciLifeLab, Tomtebodavägen 23A, 17165 Solna, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Pernemalm
authors.affiliation: Faculty Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Wolfson Molecular Imaging Centre, Manchester M20 3LJ, UK.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Crosbie
authors.affiliation: Faculty Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Wolfson Molecular Imaging Centre, Manchester M20 3LJ, UK.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Whetton
mesh_terms: D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D057285:Precision Medicine / Q000379:methods; D011379:Prognosis; D015398:Signal Transduction
keywords: Biomarkers; Cancer stem cells; Epidermal growth factor receptor (EGFR); Lung cancer; Molecular histology; Personalised medicine