oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciencesoncotomsk-255Research ArticleОБЗОРЫREVIEWSМолекулярная патология рака легкого: клинические аспектыMolecular pathology of lung cancer: clinical aspectsПоляковИ. С.PolyakovI. S.ИмянитовЕ. Н.ImyanitovE. N.evgeny@imyanitov.spb.ruКраевая клиническая больница № 1 им. проф. С.В. Очаповского, г. Краснодар, Кубанский государственный медицинский университет, г. КраснодарРоссияS.V. Ochapovskiy Regional Clinical Hospital, Krasnodar,Kuban Medical University, KrasnodarRussian FederationНИИ онкологии им. Н.Н. Петрова, Санкт-Петербургский государственный педиатрический медицинский университет,Северо-Западный государственный медицинский университет им. И.И. МечниковаРоссияN.N. Petrov Institute of Oncology, St.-Petersburg Pediatric Medical University, I.I. Mechnikov North-West Medical UniversityRussian Federation201325022016164855Copyright © Поляков И.С., Имянитов Е.Н., 20162016Поляков И.С., Имянитов Е.Н.Polyakov I.S., Imyanitov E.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/255

Обнаружение мутаций, ассоциированных с беспрецедентной чувствительностью карцином лёгкого к ингибиторам тирозинкиназ, представляется наиболее важным событием клинической онкологии в прошедшем десятилетии. Активирующие повреждения в гене, кодирующем рецептор эпидермального фактора роста (EGFR), практически гарантируют ответ на лечение гефитинибом, эрлотинибом или афатинибом. Перестройки гена ALK ассоциированы с выраженным эффектом на терапию кризотинибом или другими ALK-ингибиторами. Продемонстрирована результативность таргетной терапии по отношению к опухолям, содержащим мутации в генах ROS1, RET, HER2, BRAF и KRAS. Изучение карцином лёгкого посредством полногеномного секвенирования позволило выявить новые перспективные мишени для лечебных воздействий. Тенденции накопления сведений о молекулярном патогенезе РЛ дают основания полагать, что спектр потенциально эффективных таргетных препаратов для лечения РЛ многократно расширится уже в этом десятилетии

Discovery of tyrosine kinase inhibitor sensitizing mutations in lung cancer (LC) appears to be the main event in clinical oncology of the last decade. Activating lesions in epidermal growth factor receptor (EGFR) gene almost guarantee tumor response to gefitinib, erlotinib or afatinib.ALK translocations are strongly associated with efficacy of crizotinib or otherALK inhibitors. Instances of success of targeted therapy have been demonstrated for LC harboring mutations in ROS1, RET, HER2, BRAF and KRAS oncogenes. Whole genome sequencing of LC-derived DNAhas revealed a number of novel potentially druggable molecules. Rapid progress in understanding of lung cancer molecular pathogenesis allows to expect that several new targeted agents for LC treatment will become available already within this decade.

рак лёгкогомутациитаргетная терапияlung cancermutationstargeted therapyReferencesAlexandrov L.B., Nik-Zainal S., Wedge D.C. et al. Signatures of mutational processes in human cancer//Nature. 2013. Vol. 500 (7463). P. 415-421Alexandrov L.B., Nik-Zainal S., Wedge D.C. et al. Signatures of mutational processes in human cancer//Nature. 2013. Vol. 500 (7463). P. 415-421Bauml J., Mick R., Zhang Y. et al. Frequency of EGFR and KRAS mutations in patients with non small cell lung cancer by racial background: Do disparities exist?//Lung Cancer. 2013. Vol. 81. P. 347-353Bauml J., Mick R., Zhang Y. et al. Frequency of EGFR and KRAS mutations in patients with non small cell lung cancer by racial background: Do disparities exist?//Lung Cancer. 2013. Vol. 81. P. 347-353Boch C., Kollmeier J., Roth A. et al. The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): routine screening data for central Europe from a cohort study//BMJ Open. 2013. Vol. 3. P. e002560Boch C., Kollmeier J., Roth A. et al. The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): routine screening data for central Europe from a cohort study//BMJ Open. 2013. Vol. 3. P. e002560Bos M., Gardizi M., Schildhaus H.U. et al. Complete metabolic response in a patient with repeatedly relapsed non-small cell lung cancer harboring ROS1 gene rearrangement after treatment with crizotinib//Lung Cancer. 2013. Vol. 81. P. 142-143Bos M., Gardizi M., Schildhaus H.U. et al. Complete metabolic response in a patient with repeatedly relapsed non-small cell lung cancer harboring ROS1 gene rearrangement after treatment with crizotinib//Lung Cancer. 2013. Vol. 81. P. 142-143Burton A. What went wrong with Iressa?//Lancet Oncol. 2002. Vol. 3. P. 708Burton A. What went wrong with Iressa?//Lancet Oncol. 2002. Vol. 3. P. 708Camidge D.R., Bang Y.J., Kwak E.L. et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study//Lancet Oncol. 2012. Vol. 13. P. 1011-1019Camidge D.R., Bang Y.J., Kwak E.L. et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study//Lancet Oncol. 2012. Vol. 13. P. 1011-1019Cancer GenomeAtlas ResearchNetwork.Comprehensivegenomic characterization of squamous cell lung cancers//Nature. 2012. Vol. 489. P. 519-525Cancer GenomeAtlas ResearchNetwork.Comprehensivegenomic characterization of squamous cell lung cancers//Nature. 2012. Vol. 489. P. 519-525Cohen M.H., Williams G.A., Sridhara R. et al. FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets//Oncologist. 2003. Vol. 8. P. 303-306Cohen M.H., Williams G.A., Sridhara R. et al. FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets//Oncologist. 2003. Vol. 8. P. 303-306D’Angelo S.P., Janjigian Y.Y., Ahye N. et al. Distinct clinical course of EGFR-mutant resected lung cancers: results of testing of 1118 surgical specimens and effects of adjuvant gefitinib and erlotinib//J. Thorac. Oncol. 2012. Vol. 7. P. 1815-1822D’Angelo S.P., Janjigian Y.Y., Ahye N. et al. Distinct clinical course of EGFR-mutant resected lung cancers: results of testing of 1118 surgical specimens and effects of adjuvant gefitinib and erlotinib//J. Thorac. Oncol. 2012. Vol. 7. P. 1815-1822D’Arcangelo M., Wynes M.W., Hirsch F.R. et al. The role of anaplastic lymphoma kinase inhibitors in the treatment of advanced nonsmall cell lung cancer//Curr. Opin. Oncol. 2013. Vol. 25. P. 121-129D’Arcangelo M., Wynes M.W., Hirsch F.R. et al. The role of anaplastic lymphoma kinase inhibitors in the treatment of advanced nonsmall cell lung cancer//Curr. Opin. Oncol. 2013. Vol. 25. P. 121-129Ding L., Getz G., Wheeler D.A. et al. Somatic mutations affect key pathways in lung adenocarcinoma//Nature. 2008. Vol. 455. P. 1069-1075Ding L., Getz G., Wheeler D.A. et al. Somatic mutations affect key pathways in lung adenocarcinoma//Nature. 2008. Vol. 455. P. 1069-1075Doebele R.C., Pilling A.B., Aisner D.L. et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer//Clin. Cancer Res. 2012. Vol. 18. P. 1472-1482Doebele R.C., Pilling A.B., Aisner D.L. et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer//Clin. Cancer Res. 2012. Vol. 18. P. 1472-1482Drilon A., Rekhtman N., Ladanyi M., Paik P. Squamous-cell carcinomas of the lung: emerging biology, controversies, and the promise of targeted therapy//Lancet Oncol. 2012. Vol. 13. E. 418-426Drilon A., Rekhtman N., Ladanyi M., Paik P. Squamous-cell carcinomas of the lung: emerging biology, controversies, and the promise of targeted therapy//Lancet Oncol. 2012. Vol. 13. E. 418-426Fukui T., Yatabe Y., Kobayashi Y. et al. Clinicoradiologic characteristics of patients with lung adenocarcinoma harboring EML4-ALK fusion oncogene//Lung Cancer. 2012. Vol. 77. P. 319-325Fukui T., Yatabe Y., Kobayashi Y. et al. Clinicoradiologic characteristics of patients with lung adenocarcinoma harboring EML4-ALK fusion oncogene//Lung Cancer. 2012. Vol. 77. P. 319-325Fukuoka M., Wu Y.L., Thongprasert S. et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS)//J. Clin. Oncol. 2011. Vol. 29. P. 2866-2874Fukuoka M., Wu Y.L., Thongprasert S. et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS)//J. Clin. Oncol. 2011. Vol. 29. P. 2866-2874Garraway L.A., Lander E.S. Lessons from the cancer genome//Cell. 2013. Vol. 153. P. 17-37Garraway L.A., Lander E.S. Lessons from the cancer genome//Cell. 2013. Vol. 153. P. 17-37Gautschi O., Pauli C., Strobel K. et al. Apatient with BRAF V600E lung adenocarcinoma responding to vemurafenib//J. Thorac. Oncol. 2012. Vol. 7. P. e23-e24Gautschi O., Pauli C., Strobel K. et al. Apatient with BRAF V600E lung adenocarcinoma responding to vemurafenib//J. Thorac. Oncol. 2012. Vol. 7. P. e23-e24Giaccone G., Herbst R.S., Manegold C. et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 1//J. Clin. Oncol. 2004. Vol. 22. P. 777-784Giaccone G., Herbst R.S., Manegold C. et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 1//J. Clin. Oncol. 2004. Vol. 22. P. 777-784Goto K., Nishio M., Yamamoto N. et al. A prospective, phase II, open-label study (JO22903) of first-line erlotinib in Japanese patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC)//Lung Cancer. 2013. Vol. 82 (1). P. 109-114Goto K., Nishio M., Yamamoto N. et al. A prospective, phase II, open-label study (JO22903) of first-line erlotinib in Japanese patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC)//Lung Cancer. 2013. Vol. 82 (1). P. 109-114Govindan R., Ding L., Griffith M. et al. Genomic landscape of non-small cell lung cancer in smokers and never-smokers//Cell. 2012. Vol. 150. P. 1121-1134Govindan R., Ding L., Griffith M. et al. Genomic landscape of non-small cell lung cancer in smokers and never-smokers//Cell. 2012. Vol. 150. P. 1121-1134Herbst R.S., Giaccone G., Schiller J.H. et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 2//J. Clin. Oncol. 2004. Vol. 22. P. 785-794Herbst R.S., Giaccone G., Schiller J.H. et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 2//J. Clin. Oncol. 2004. Vol. 22. P. 785-794Imielinski M., Berger A.H., Hammerman P.S. et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing//Cell. 2012. Vol. 150. P. 1107-1120Imielinski M., Berger A.H., Hammerman P.S. et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing//Cell. 2012. Vol. 150. P. 1107-1120Inoue A., Kobayashi K., Maemondo M. et al. Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002)//Ann. Oncol. 2013. Vol. 24. P. 54-59Inoue A., Kobayashi K., Maemondo M. et al. Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002)//Ann. Oncol. 2013. Vol. 24. P. 54-59Jakobsen J.N., Sørensen J.B. Intratumor heterogeneity and chemotherapy-induced changes in EGFR status in non-small cell lung cancer//Cancer. Chemother. Pharmacol. 2012. Vol. 69. P. 289-299Jakobsen J.N., Sørensen J.B. Intratumor heterogeneity and chemotherapy-induced changes in EGFR status in non-small cell lung cancer//Cancer. Chemother. Pharmacol. 2012. Vol. 69. P. 289-299Jänne P.A., Shaw A.T., Pereira J.R. et al. Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study//Lancet Oncol. 2013. Vol. 14. P. 38-47Jänne P.A., Shaw A.T., Pereira J.R. et al. Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study//Lancet Oncol. 2013. Vol. 14. P. 38-47Katakami N., Atagi S., Goto K. et al. LUX-Lung 4: A phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both//J. Clin. Oncol. 2013 (in press)Katakami N., Atagi S., Goto K. et al. LUX-Lung 4: A phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both//J. Clin. Oncol. 2013 (in press)Komiya T., Thomas A., Khozin S. et al. Response to crizotinib in ROS1-rearranged non-small-cell lung cancer//J. Clin. Oncol. 2012. Vol. 30. P. 3425-3426Komiya T., Thomas A., Khozin S. et al. Response to crizotinib in ROS1-rearranged non-small-cell lung cancer//J. Clin. Oncol. 2012. Vol. 30. P. 3425-3426Ku G.Y., Haaland B.A., de Lima Lopes G. Jr. Gefitinib vs. chemotherapy as first-line therapy in advanced non-small cell lung cancer: metaanalysis of phase III trials//Lung Cancer. 2011. Vol. 74. P. 469-473Ku G.Y., Haaland B.A., de Lima Lopes G. Jr. Gefitinib vs. chemotherapy as first-line therapy in advanced non-small cell lung cancer: metaanalysis of phase III trials//Lung Cancer. 2011. Vol. 74. P. 469-473Kwak E.L., Bang Y.J., Camidge D.R. et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer//N. Engl. J. Med. 2010. Vol. 363. P. 1693-1703Kwak E.L., Bang Y.J., Camidge D.R. et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer//N. Engl. J. Med. 2010. Vol. 363. P. 1693-1703Levchenko E.V., Moiseyenko V.M., Matsko D.E. et al. Down-staging of EGFR mutation-positive advanced lung carcinoma with gefitinib followed by surgical intervention: follow-up of two cases//Onkologie. 2009. Vol. 32. P. 674-677Levchenko E.V., Moiseyenko V.M., Matsko D.E. et al. Down-staging of EGFR mutation-positive advanced lung carcinoma with gefitinib followed by surgical intervention: follow-up of two cases//Onkologie. 2009. Vol. 32. P. 674-677Liao R.G., Jung J., Tchaicha J. et al. Inhibitor-sensitive FGFR2 and FGFR3 mutations in lung squamous cell carcinoma//Cancer Res. 2013. Vol. 73. P. 5195-5205Liao R.G., Jung J., Tchaicha J. et al. Inhibitor-sensitive FGFR2 and FGFR3 mutations in lung squamous cell carcinoma//Cancer Res. 2013. Vol. 73. P. 5195-5205Lim S.M., Kim H.R., Shim H.S. et al. Role of FGF receptors as an emerging therapeutic target in lung squamous cell carcinoma//Future Oncol. 2013. Vol. 9. P. 377-386Lim S.M., Kim H.R., Shim H.S. et al. Role of FGF receptors as an emerging therapeutic target in lung squamous cell carcinoma//Future Oncol. 2013. Vol. 9. P. 377-386Lindeman N.I., Cagle P.T., Beasley M.B. et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology//J. Thorac. Oncol. 2013. Vol. 8. P. 823-859Lindeman N.I., Cagle P.T., Beasley M.B. et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology//J. Thorac. Oncol. 2013. Vol. 8. P. 823-859Lipson D., Capelletti M., Yelensky R. et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies//Nat. Med. 2012. Vol. 18. P. 382-384Lipson D., Capelletti M., Yelensky R. et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies//Nat. Med. 2012. Vol. 18. P. 382-384Lynch T.J., Bell D.W., Sordella R. 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. Vol. 350. P. 2129-2139Lynch T.J., Bell D.W., Sordella R. 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. Vol. 350. P. 2129-2139Maemondo M., Inoue A., Kobayashi K. et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR//N. Engl. J. Med. 2010. Vol. 362. P. 2380-2388Maemondo M., Inoue A., Kobayashi K. et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR//N. Engl. J. Med. 2010. Vol. 362. P. 2380-2388Marchetti A., Felicioni L., Malatesta S. et al. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations//J. Clin. Oncol. 2011. Vol. 29. P. 3574-3579Marchetti A., Felicioni L., Malatesta S. et al. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations//J. Clin. Oncol. 2011. Vol. 29. P. 3574-3579Mattsson J.S., Imgenberg-Kreuz J., Edlund K. et al. Consistent mutation status within histologically heterogeneous lung cancer lesions//Histopathology. 2012. Vol. 61. P. 744-748Mattsson J.S., Imgenberg-Kreuz J., Edlund K. et al. Consistent mutation status within histologically heterogeneous lung cancer lesions//Histopathology. 2012. Vol. 61. P. 744-748Mazières J., Peters S., Lepage B. et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives//J. Clin. Oncol. 2013. Vol. 31. P. 1997-2003Mazières J., Peters S., Lepage B. et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives//J. Clin. Oncol. 2013. Vol. 31. P. 1997-2003Miller V.A., Hirsh V., Cadranel J. et al. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1P.) a phase 2b/3 randomised trial//Lancet Oncol. 2012. Vol. 13. P. 528-538Miller V.A., Hirsh V., Cadranel J. et al. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1P.) a phase 2b/3 randomised trial//Lancet Oncol. 2012. Vol. 13. P. 528-538Mitiushkina N.V., Iyevleva A.G., Poltoratskiy A.N. et al. Detection of EGFR mutations and EML4-ALK rearrangements in lung adenocarcinomas using archived cytological slides//Cancer Cytopathol. 2013. Vol. 121. P. 370-376Mitiushkina N.V., Iyevleva A.G., Poltoratskiy A.N. et al. Detection of EGFR mutations and EML4-ALK rearrangements in lung adenocarcinomas using archived cytological slides//Cancer Cytopathol. 2013. Vol. 121. P. 370-376Mitsudomi T., Morita S., Yatabe Y. et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405P.) an open label, randomised phase 3 trial//Lancet Oncol. 2010. Vol. 11. P. 121-128Mitsudomi T., Morita S., Yatabe Y. et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405P.) an open label, randomised phase 3 trial//Lancet Oncol. 2010. Vol. 11. P. 121-128Moiseyenko V.M., Procenko S.A., Levchenko E.V. et al. High efficacy of first-line gefitinib in non-Asian patients with EGFR-mutated lung adenocarcinoma//Onkologie. 2010. Vol. 33. P. 231-238Moiseyenko V.M., Procenko S.A., Levchenko E.V. et al. High efficacy of first-line gefitinib in non-Asian patients with EGFR-mutated lung adenocarcinoma//Onkologie. 2010. Vol. 33. P. 231-238Mok T.S., Wu Y.L., Thongprasert S. et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma//N. Engl. J. Med. 2009. Vol. 361. P. 947-957Mok T.S., Wu Y.L., Thongprasert S. et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma//N. Engl. J. Med. 2009. Vol. 361. P. 947-957Murakami Y., Mitsudomi T., Yatabe Y. A Screening Method for the ALK Fusion Gene in NSCLC//Front Oncol. 2012. Vol. 2. P. 24Murakami Y., Mitsudomi T., Yatabe Y. A Screening Method for the ALK Fusion Gene in NSCLC//Front Oncol. 2012. Vol. 2. P. 24Nagashima O., Ohashi R., Yoshioka Y. et al. High prevalence of gene abnormalities in young patients with lung cancer//J. Thorac. Dis. 2013. Vol. 5. P. 27-30Nagashima O., Ohashi R., Yoshioka Y. et al. High prevalence of gene abnormalities in young patients with lung cancer//J. Thorac. Dis. 2013. Vol. 5. P. 27-30Nurwidya F., Murakami A., Takahashi F., Takahashi K. Molecular mechanisms contributing to resistance to tyrosine kinase-targeted therapy for non-small cell lung cancer//Cancer Biol. Med. 2012. Vol. 9. P. 18-22Nurwidya F., Murakami A., Takahashi F., Takahashi K. Molecular mechanisms contributing to resistance to tyrosine kinase-targeted therapy for non-small cell lung cancer//Cancer Biol. Med. 2012. Vol. 9. P. 18-22Oh I.J., Ban H.J., Kim K.S. et al. Retreatment of gefitinib in patients with non-small-cell lung cancer who previously controlled to gefitinib: a single-arm, open-label, phase II study//Lung Cancer. 2012. Vol. 77. P. 121-127Oh I.J., Ban H.J., Kim K.S. et al. Retreatment of gefitinib in patients with non-small-cell lung cancer who previously controlled to gefitinib: a single-arm, open-label, phase II study//Lung Cancer. 2012. Vol. 77. P. 121-127Oxnard G.R., Miller V.A., Robson M.E. et al. Screening for germ-line EGFR T790M mutations through lung cancer genotyping//J. Thorac. Oncol. 2012. Vol. 7. P. 1049-1052Oxnard G.R., Miller V.A., Robson M.E. et al. Screening for germ-line EGFR T790M mutations through lung cancer genotyping//J. Thorac. Oncol. 2012. Vol. 7. P. 1049-1052Paez J.G., Jänne P.A., Lee J.C. et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy//Science. 2004. Vol. 304. P. 1497-1500Paez J.G., Jänne P.A., Lee J.C. et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy//Science. 2004. Vol. 304. P. 1497-1500Pao W., Girard N. New driver mutations in non-small-cell lung cancer//Lancet Oncol. 2011. Vol. 12. P. 175-180Pao W., Girard N. New driver mutations in non-small-cell lung cancer//Lancet Oncol. 2011. Vol. 12. P. 175-180Pao W., Miller V., Zakowski M. et al. EGF receptor gene mutations are common in lung cancers from „never smokers“ and are associated with sensitivity of tumors to gefitinib and erlotinib//Proc. Natl. Acad. Sci. USA. 2004. Vol. 101. P. 13306-13311Pao W., Miller V., Zakowski M. et al. EGF receptor gene mutations are common in lung cancers from „never smokers“ and are associated with sensitivity of tumors to gefitinib and erlotinib//Proc. Natl. Acad. Sci. USA. 2004. Vol. 101. P. 13306-13311Pillai R.N., Ramalingam S.S. The biology and clinical features of non-small cell lung cancers with EML4-ALK translocation//Curr. Oncol. Rep. 2012. Vol. 14. P. 105-110Pillai R.N., Ramalingam S.S. The biology and clinical features of non-small cell lung cancers with EML4-ALK translocation//Curr. Oncol. Rep. 2012. Vol. 14. P. 105-110Pleasance E.D., Stephens P.J., O’Meara S. et al. A small-cell lung cancer genome with complex signatures of tobacco exposure//Nature. 2010. Vol. 463. P. 184-190Pleasance E.D., Stephens P.J., O’Meara S. et al. A small-cell lung cancer genome with complex signatures of tobacco exposure//Nature. 2010. Vol. 463. P. 184-190Ranson M., Hammond L.A., Ferry D. et al. ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial//J. Clin. Oncol. 2002. Vol. 20. P. 2240-2250Ranson M., Hammond L.A., Ferry D. et al. ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial//J. Clin. Oncol. 2002. Vol. 20. P. 2240-2250Rikova K., Guo A., Zeng Q. et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer//Cell. 2007. Vol. 131. P. 1190-1203Rikova K., Guo A., Zeng Q. et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer//Cell. 2007. Vol. 131. P. 1190-1203Rosell R., Moran T., Queralt C. et al. Screening for epidermal growth factor receptor mutations in lung cancer//N. Engl. J. Med. 2009. Vol. 361. P. 958-967Rosell R., Moran T., Queralt C. et al. Screening for epidermal growth factor receptor mutations in lung cancer//N. Engl. J. Med. 2009. Vol. 361. P. 958-967Seto T., Kiura K., Nishio M. et al. CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF001JP study): a single-arm, open-label, phase 1-2 study//Lancet Oncol. 2013. Vol. 14. P. 590-598Seto T., Kiura K., Nishio M. et al. CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF001JP study): a single-arm, open-label, phase 1-2 study//Lancet Oncol. 2013. Vol. 14. P. 590-598Sequist L.V., Yang J.C., Yamamoto N. et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations//J. Clin. Oncol. 2013. Vol. 31 (27). P. 3327-3334Sequist L.V., Yang J.C., Yamamoto N. et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations//J. Clin. Oncol. 2013. Vol. 31 (27). P. 3327-3334Shaw A.T., Engelman J.A. ALK in lung cancer: past, present, and future//J. Clin. Oncol. 2013. Vol. 31. P. 1105-1111Shaw A.T., Engelman J.A. ALK in lung cancer: past, present, and future//J. Clin. Oncol. 2013. Vol. 31. P. 1105-1111Shaw A.T., Kim D.W., Nakagawa K. et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer//N. Engl. J. Med. 2013. Vol. 368. P. 2385-2394Shaw A.T., Kim D.W., Nakagawa K. et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer//N. Engl. J. Med. 2013. Vol. 368. P. 2385-2394Shaw A.T., Yeap B.Y., Solomon B.J. et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis//Lancet Oncol. 2011. Vol. 12. P. 1004-1012Shaw A.T., Yeap B.Y., Solomon B.J. et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis//Lancet Oncol. 2011. Vol. 12. P. 1004-1012Shigematsu H., Lin L., Takahashi T. et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers//J. Natl. Cancer Inst. 2005. Vol. 97. P. 339-346Shigematsu H., Lin L., Takahashi T. et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers//J. Natl. Cancer Inst. 2005. Vol. 97. P. 339-346Soda M., Choi Y.L., Enomoto M. et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer//Nature. 2007. Vol. 448. P. 561-566Soda M., Choi Y.L., Enomoto M. et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer//Nature. 2007. Vol. 448. P. 561-566Suspitsin E.N., Levchenko E.V., Moiseyenko F.V. et al. Rapid symptomatic improvement in gefitinib-treated patients with EGFR-mutated lung cancer: possible role of downregulation of inflammatory molecules?//Onkologie. 2011. Vol. 34. P. 559-560Suspitsin E.N., Levchenko E.V., Moiseyenko F.V. et al. Rapid symptomatic improvement in gefitinib-treated patients with EGFR-mutated lung cancer: possible role of downregulation of inflammatory molecules?//Onkologie. 2011. Vol. 34. P. 559-560Takahashi R., Hirata H., Tachibana I. et al. Early [18F]fluorodeoxyglucose positron emission tomography at two days of gefitinib treatment predicts clinical outcome in patients with adenocarcinoma of the lung//Clin. Cancer Res. 2012. Vol. 18. P. 220-228Takahashi R., Hirata H., Tachibana I. et al. Early [18F]fluorodeoxyglucose positron emission tomography at two days of gefitinib treatment predicts clinical outcome in patients with adenocarcinoma of the lung//Clin. Cancer Res. 2012. Vol. 18. P. 220-228Takeuchi K., Soda M., Togashi Y. et al. RET, ROS1 and ALK fusions in lung cancer//Nat. Med. 2012. Vol. 18. P. 378-381Takeuchi K., Soda M., Togashi Y. et al. RET, ROS1 and ALK fusions in lung cancer//Nat. Med. 2012. Vol. 18. P. 378-381Tanizaki J., Okamoto I., Okabe T. et al. Activation of HER family signaling as a mechanism of acquired resistance to ALK inhibitors in EML4-ALK-positive non-small cell lung cancer//Clin. Cancer Res. 2012. Vol. 18. P. 6219-6226Tanizaki J., Okamoto I., Okabe T. et al. Activation of HER family signaling as a mechanism of acquired resistance to ALK inhibitors in EML4-ALK-positive non-small cell lung cancer//Clin. Cancer Res. 2012. Vol. 18. P. 6219-6226Thunnissen E., Bubendorf L., Dietel M. et al. EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations//Virchows Arch. 2012. Vol. 461. P. 245-257Thunnissen E., Bubendorf L., Dietel M. et al. EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations//Virchows Arch. 2012. Vol. 461. P. 245-257van Noesel J., van der Ven W.H., van Os T.A. et al. Activatinggermline R776H mutation in the epidermal growth factor receptor associated with lung cancer with squamous differentiation//J. Clin. Oncol. 2013. Vol. 31. E. 161-164van Noesel J., van der Ven W.H., van Os T.A. et al. Activatinggermline R776H mutation in the epidermal growth factor receptor associated with lung cancer with squamous differentiation//J. Clin. Oncol. 2013. Vol. 31. E. 161-164Wang R., Pan Y., Li C. et al. The use of quantitative real-time reverse transcriptase PCR for 5‘ and 3‘ portions of ALK transcripts to detect ALK rearrangements in lung cancers//Clin Cancer Res. 2012. Vol. 18. P. 4725-4732Wang R., Pan Y., Li C. et al. The use of quantitative real-time reverse transcriptase PCR for 5‘ and 3‘ portions of ALK transcripts to detect ALK rearrangements in lung cancers//Clin Cancer Res. 2012. Vol. 18. P. 4725-4732Yu H.A., Arcila M.E., Rekhtman N. et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers//Clin. Cancer Res. 2013. Vol. 19. P. 2240-2247Yu H.A., Arcila M.E., Rekhtman N. et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers//Clin. Cancer Res. 2013. Vol. 19. P. 2240-2247

The authors declare that there are no conflicts of interest present.