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Review
. 2015 May 26;7(2):930-49.
doi: 10.3390/cancers7020816.

Targeted Therapies in Non-Small Cell Lung Cancer-Beyond EGFR and ALK

Sacha I Rothschild  1
Affiliations
Review

Targeted Therapies in Non-Small Cell Lung Cancer-Beyond EGFR and ALK

Sacha I Rothschild. Cancers (Basel). .

Abstract

Systemic therapy for non-small cell lung cancer (NSCLC) has undergone a dramatic paradigm shift over the past decade. Advances in our understanding of the underlying biology of NSCLC have revealed distinct molecular subtypes. A substantial proportion of NSCLC depends on oncogenic molecular aberrations (so-called "driver mutations") for their malignant phenotype. Personalized therapy encompasses the strategy of matching these subtypes with effective targeted therapies. EGFR mutations and ALK translocation are the most effectively targeted oncogenes in NSCLC. EGFR mutations and ALK gene rearrangements are successfully being targeted with specific tyrosine kinase inhibitors. The number of molecular subgroups of NSCLC continues to grow. The scope of this review is to discuss recent data on novel molecular targets as ROS1, BRAF, KRAS, HER2, c-MET, RET, PIK3CA, FGFR1 and DDR2. Thereby the review will focus on therapeutic strategies targeting these aberrations. Moreover, the emerging challenge of acquired resistance to initially effective therapies will be discussed.

Keywords: BRAF; DDR2; FGFR1; HER2; RET; ROS1; c-MET; lung cancer; oncogene; targeted cancer therapy.

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References

    1. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2015. CA Cancer J. Clin. 2015;65:5–29. doi: 10.3322/caac.21254. - DOI - PubMed
    1. Travis W., Brambilla E., Mueller-Hermelink H., Harris C., Harris C., editors. Pathology and Genetics: Tumours of the Lung, Pleura, Thymus and Heart. 3rd ed. Volume 10 World Health Organization Classification of Tumours, WHO; Geneva, Switzerland: 2004.
    1. Paez J.G., Janne P.A., Lee J.C., Tracy S., Greulich H., Gabriel S., Herman P., Kaye F.J., Lindeman N., Boggon T.J., et al. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science. 2004;304:1497–1500. doi: 10.1126/science.1099314. - DOI - PubMed
    1. Lynch T.J., Bell D.W., Sordella R., Gurubhagavatula S., Okimoto R.A., Brannigan B.W., Harris P.L., Haserlat S.M., Supko J.G., Haluska F.G., et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 2004;350:2129–2139. doi: 10.1056/NEJMoa040938. - DOI - PubMed
    1. Kwak E.L., Bang Y.J., Camidge D.R., Shaw A.T., Solomon B., Maki R.G., Ou S.H., Dezube B.J., Janne P.A., Costa D.B., et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N. Engl. J. Med. 2010;363:1693–1703. doi: 10.1056/NEJMoa1006448. - DOI - PMC - PubMed