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Молекулярная патология рака легкого: клинические аспекты

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Аннотация

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

Об авторах

И. С. Поляков
Краевая клиническая больница № 1 им. проф. С.В. Очаповского, г. Краснодар, Кубанский государственный медицинский университет, г. Краснодар
Россия


Е. Н. Имянитов
НИИ онкологии им. Н.Н. Петрова, Санкт-Петербургский государственный педиатрический медицинский университет,Северо-Западный государственный медицинский университет им. И.И. Мечникова
Россия


Список литературы

1. Alexandrov L.B., Nik-Zainal S., Wedge D.C. et al. Signatures of mutational processes in human cancer//Nature. 2013. Vol. 500 (7463). P. 415-421

2. Bauml 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. 347-353

3. Boch 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. e002560

4. Bos 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. 142-143

5. Burton A. What went wrong with Iressa?//Lancet Oncol. 2002. Vol. 3. P. 708

6. Camidge 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. 1011-1019

7. Cancer GenomeAtlas ResearchNetwork.Comprehensivegenomic characterization of squamous cell lung cancers//Nature. 2012. Vol. 489. P. 519-525

8. Cohen M.H., Williams G.A., Sridhara R. et al. FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets//Oncologist. 2003. Vol. 8. P. 303-306

9. D’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. 1815-1822

10. D’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. 121-129

11. Ding L., Getz G., Wheeler D.A. et al. Somatic mutations affect key pathways in lung adenocarcinoma//Nature. 2008. Vol. 455. P. 1069-1075

12. Doebele 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. 1472-1482

13. Drilon 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. 418-426

14. Fukui 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. 319-325

15. Fukuoka 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. 2866-2874

16. Garraway L.A., Lander E.S. Lessons from the cancer genome//Cell. 2013. Vol. 153. P. 17-37

17. Gautschi O., Pauli C., Strobel K. et al. Apatient with BRAF V600E lung adenocarcinoma responding to vemurafenib//J. Thorac. Oncol. 2012. Vol. 7. P. e23-e24

18. Giaccone 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. 777-784

19. Goto 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. 109-114

20. Govindan 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. 1121-1134

21. Herbst 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. 785-794

22. Imielinski M., Berger A.H., Hammerman P.S. et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing//Cell. 2012. Vol. 150. P. 1107-1120

23. Inoue 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. 54-59

24. Jakobsen 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. 289-299

25. Jänne 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. 38-47

26. 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)

27. 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. 3425-3426

28. Ku 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. 469-473

29. Kwak 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. 1693-1703

30. Levchenko 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. 674-677

31. Liao 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. 5195-5205

32. Lim 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. 377-386

33. Lindeman 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. 823-859

34. Lipson 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. 382-384

35. Lynch 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. 2129-2139

36. Maemondo 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. 2380-2388

37. Marchetti 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. 3574-3579

38. Mattsson J.S., Imgenberg-Kreuz J., Edlund K. et al. Consistent mutation status within histologically heterogeneous lung cancer lesions//Histopathology. 2012. Vol. 61. P. 744-748

39. Mazières 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. 1997-2003

40. Miller 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. 528-538

41. Mitiushkina 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. 370-376

42. Mitsudomi 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. 121-128

43. Moiseyenko 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. 231-238

44. Mok T.S., Wu Y.L., Thongprasert S. et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma//N. Engl. J. Med. 2009. Vol. 361. P. 947-957

45. Murakami Y., Mitsudomi T., Yatabe Y. A Screening Method for the ALK Fusion Gene in NSCLC//Front Oncol. 2012. Vol. 2. P. 24

46. Nagashima 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. 27-30

47. Nurwidya 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. 18-22

48. Oh 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. 121-127

49. Oxnard 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. 1049-1052

50. Paez 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. 1497-1500

51. Pao W., Girard N. New driver mutations in non-small-cell lung cancer//Lancet Oncol. 2011. Vol. 12. P. 175-180

52. Pao 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. 13306-13311

53. Pillai 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. 105-110

54. Pleasance 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. 184-190

55. Ranson 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. 2240-2250

56. Rikova K., Guo A., Zeng Q. et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer//Cell. 2007. Vol. 131. P. 1190-1203

57. Rosell 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. 958-967

58. Seto 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. 590-598

59. Sequist 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. 3327-3334

60. Shaw A.T., Engelman J.A. ALK in lung cancer: past, present, and future//J. Clin. Oncol. 2013. Vol. 31. P. 1105-1111

61. Shaw 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. 2385-2394

62. Shaw 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. 1004-1012

63. Shigematsu 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. 339-346

64. Soda 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. 561-566

65. Suspitsin 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. 559-560

66. Takahashi 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. 220-228

67. Takeuchi K., Soda M., Togashi Y. et al. RET, ROS1 and ALK fusions in lung cancer//Nat. Med. 2012. Vol. 18. P. 378-381

68. Tanizaki 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. 6219-6226

69. Thunnissen 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. 245-257

70. van 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. 161-164

71. Wang 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. 4725-4732

72. Yu 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


Для цитирования:


Поляков И.С., Имянитов Е.Н. Молекулярная патология рака легкого: клинические аспекты. Сибирский онкологический журнал. 2013;1(6):48-55.

For citation:


Polyakov I.S., Imyanitov E.N. Molecular pathology of lung cancer: clinical aspects. Siberian journal of oncology. 2013;1(6):48-55. (In Russ.)

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