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Non-small-cell lung cancers: a heterogeneous set of diseases
Zhao Chen1*, Christine M.Fillmore2,3,4*, Peter S.Hammerman1, Carla F.Kim2,3,4 and Kwok-Kin Wong1,5,6
Abstract | Non-small-cell lung cancers (NSCLCs), the most common lung cancers, are known to have diverse pathological features. During the past decade, in-depth analyses of lung cancer genomes and signalling pathways have further defined NSCLCs as a group of distinct diseases with genetic and cellular heterogeneity. Consequently, an impressive list of potential therapeutic targets was unveiled, drastically altering the clinical evaluation and treatment of patients. Many targeted therapies have been developed with compelling clinical proofs of concept; however, treatment responses are typically short-lived. Further studies of the tumour microenvironment have uncovered new possible avenues to control this deadly disease, including immunotherapy.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Stem Cell Program, Boston Childrens Hospital, Boston, Massachusetts 02115, USA.
Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA.
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. *These authors contributed equally to this work. Correspondence to P.S.H., C.F.K.and K.-K.W.e-mails: mailto:phammerman%40partners.org?subject=
Web End =phammerman@ mailto:phammerman%40partners.org?subject=
Web End =partners.org ; mailto:carla.kim%40childrens.harvard.edu?subject=
Web End =carla.kim@ mailto:carla.kim%40childrens.harvard.edu?subject=
Web End =childrens.harvard.edu ; mailto:kwong1%40partners.org?subject=
Web End [email protected] doi:10.1038/nrc3775
Lung cancer results in the largest number of cancer-related deaths worldwide1,2. More than 85% of those cases are currently classified as non-small-cell lung cancer (NSCLC), for which the predicted 5-year survival rate is 15.9% a figure that has only marginally improved during the past few decades3. Technological advances during the past decade, including the introduction of next-generation sequencing (NGS), the generation of multiple genetically engineered mouse models (GEMMs) of lung cancer and the construction of large databases characterizing the molecular features of human tumours, have transformed our view of NSCLC from histopathological descriptions to precise molecular and genetic identities that can be resolved to the single-cell level. In parallel, approaches and concepts from fields such as developmental biology, stem cell biology and immunology have deepened our knowledge of tumour development, cellular heterogeneity and interactions between the lung tumour and its surrounding microenvironment. These multidisciplinary efforts have enhanced our understanding of molecular disease mechanisms, thereby forming the rationales...