Classification génomique des cancers du poumon: Vers un traitement personnalisé?

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Publiée Oct 26, 2015
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Vol. 93 No 6 (2015): Revue juin 2015

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Mona Mlika
Soumeya Laabidi
Mehdi Afrit
Hamouda Boussen
Faouzi El Mezni

Résumé

Le cancer du poumon représente la première cause de décès par cancer dans le monde. Son incidence a augmenté en Tunisie de 17.6 cas/100.000 habitants en 1997 à 27.6 cas/100.000 habitants en 2003. Son pronostic est en train de s’améliorer depuis la découverte de nouvelles thérapies ciblées. La première d’entre elles est représentée par l’EGFR (Epidermal growth factor receptor) qui marque cette année (2014), son 10ème anniversaire. D’autres cibles thérapeutiques ont été identifiées et sont représentées essentiellement par le gène de fusion ALK-EML4 mais d’autres voies de la carcinogenèse sont également impliquées incluantHER2, BRAF, MET, RET…. Les plus grandes difficultés rencontréesdans le domaine de la génomique sont représentées par l’absence de réel consensus concernant les stratégies thérapeutiques,l’absence de techniques de diagnostic fiables et l’apparitioninévitable de résistances secondaires impliquant de nouvelles voies de la carcinogenèse. Dans cette mise au point, nous présentons lesvoies de la carcinogenèse les plus explorées et ciblées ainsi que lesstratégies diagnostiques adoptées en routine.

Mots-clés :

Cancer du poumon, EGFR, ALK-EML4, KRAS, Cancer du poumon, EGFR, ALK-EML4, KRAS

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Références

  1. Sequist LV, Heist RS, Shaw AT, et al. Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice. Ann Oncol 2011;22:2616-2624
  2. Kris MG, Johnson BE, Kwiatkowski DJ. Identification of driver mutations in tumor specimens from 1,000 patients with lung adenocarcinoma: the NCI's Lung Cancer Mutation Consortium (LCMC). J ClinOncol 2011;29:Abstr CRA7506.
  3. Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 2005;5:341-354. 4. Suda K, Tomizawa K, Mitsudomi T. Biological and clinical significance of KRAS mutations in lung cancer: an oncogenic driver that contrasts with EGFR mutation. Cancer Metastasis Rev 2010;29:49-60
  4. Suda K, Tomizawa K, Mitsudomi T. Biological and clinical significance of KRAS mutations in lung cancer: an oncogenic driver that contrasts with EGFR mutation. Cancer Metastasis Rev 2010;29:49-60
  5. Carr LL, Finigan JH, Kern JA. Evaluation and treatment of patients with non-small cell lung cancer. Med Clin North Am 2011;95:1041-1054
  6. Mitsudomi T, Yatabe Y. Mutations of the epidermal growth factor receptor gene and related genes as determinants of epidermal growth factor receptor tyrosine kinase inhibitors sensitivity in lung cancer. Cancer Sci 2007;98:1817-1824
  7. Berardi R, Santoni M, Morgese F, et al. Novel small molecule EGFR inhibitors as candidate drugs in non-small cell lung cancer. Onco Targets and Therapy 2013;6:563-576
  8. Parsons R. Human Cancer, PTEN and the PI-3 kinase pathway. Semin Cell DevBiol 2004;15:171-176
  9. Ng KP, Hillmer AM, Chuah CT, et al. A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. Nat Med 2012;18:521-528.
  10. Pao W, Chmielecki J. Rational, biologically based treatment of EGFRmutant non-small-cell lung cancer. Nat Rev Cancer 2010;10:760-774
  11. Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007;316:1039-43.
  12. Cataldo VD, Gibbons DL, Pérez-Soler R, et al.Treatment of non-smallcell lung cancer with erlotinib or gefitinib. N Engl J Med 2011;364:947- 55.
  13. Mao C, Qiu LX, Liao RY, et al. KRAS mutations and resistance to EGFRTKIs treatment in patient with non-small cell lung cancer: a metaanalysis of 22 studies. Lung Cancer 2010;69:272-8.
  14. Engelman JA, Chen I, Tan X, et al.Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 2008;14:1351-6.
  15. Ding L, Getz G, Wheeler DA, et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature 2008;455:1069-75.
  16. Makowski L, Hayes DN. Role of LKB1 in lung cancer development. Br J Cancer 2008;99:683-8.
  17. Vicent S, Chen R, Sayles LC, et al.Wilms Tumor 1 regulates KRASdriven oncogenesis and senescence in mouse and human models. J Clin Invest 2010;120:3940-52.
  18. Tran PT, Shroff EH, Burns TF, et al. Twist 1 suppresses senescence programs and thereby accelerates and maintains Mutant Kras-Induced lung tumorigenesis. Plos Genetics 2012;8:1-16.
  19. Soda M, Choi YL, Enomoto M, et al. Identification of the transforming ALK-EML4 fusion gene in non-small-cell lung cancer. Nature 2007;448:561-566
  20. Rikova K, Guo A, Zeng Q, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 2007;131:1190-1203.
  21. Takeuchi K, Choi YL, Togashi Y, et al. KIF5B-ALK, a novel fusion oncokinase identified by immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clin Cancer Res 2009;15:3143-3149
  22. Zhang X, Zhang S, Yang X, et al. Fusion of EML4 and ALK is assoiated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression. Mol Cancer 2010;9:188.
  23. Inamura K, Takeuchi K, Togashi Y, et al. EML4-ALK fusion is linked to histological characteristics in a subset of lung caners. J Thorac Oncol 2008;3:13-17.
  24. Thunnissen E, Budendorf L, Dietel M, et al. EML4-ALK testing in nonsmall cell carcinomas of the lung: a review and recommendations. Virchows Arch 2012;461:245-257.
  25. Murakami Y, Mitsudomi T, Yatabe Y. A screening method for the ALK fusion gene in NSCLC. Front Oncol 2012;2:24.
  26. Mino-Kenudson M, Chirieac LR, Law K, et al. A novel, highly sensitive antibody allows for the routine detection of ALK-rearranged lung adenocarcinomas by standard immunohistochemistry. Clin Cancer Res 2010;16:1561-1571.
  27. Just PA, Cazes A, Audebourg A, et al. Histologic subtypes, immunohistochemistry, FISH or molecular screening for the accurate diagnosis of ALK-rearrangement in lung cancer: a comprehensive study of Caucasian non-smokers. Lung Cancer 2012;76:309-315.
  28. Blackhall FH, Peters S, Kerr K, et al. Prevalence and clinical outcomes for patients with ALK gene rearrangement in Europe: preliminary results from the European Thoracic Oncology Platform lungsape project. Ann Oncol 2012;23:ix73-ix94.
  29. Wallander ML, Geiersbah KB, Tripp SR, Layfield LJ. Comparison of reverse transcription-poymerase chain reaction, immunohistochemistry and fluorescence in situ hybridization methodologies for detection of EML4-ALK fusion-positive non-small cell lung carcinoma: implications for optimal clinical testing. Arch Pathol Lab Med 2012;136:796-803.
  30. Sasaki T, Koivunen J, Ogino A, et al. A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Res 2011;71:6051-6060.
  31. Katayama R, Khan TM, Benes C, et al. Therapeuti strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci USA 2011;108:7535-7540.
  32. Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med 2012;4:120ra17.
  33. Doebele RC, Pilling AB, Aisner DL, et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranger non-small cell lung cancer. Clin Cancer Res 2012;18:1472-1482.
  34. Doebele RC, Aisner DL, Lee AT, et al. Analysis of resistance mechanisms to ALK kinase inhibitors in ALK+ NSCLC patients. J Clin Oncol 2012;30Suppl:7504.
  35. Ponzetto C, Bardelli A, Zhen Z, et al. A multifunctional docking site mediates signaling and transformation by the heptocyte growth factor/ scatter factor receptor family. Cell 1994;77:261-271.
  36. Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF. Met metastasis, motility and more. Nat Rev Mol Cell Biol 2003;4:915-925.
  37. Lai AZ, Abella JV, Park M. Crosstalk in Met receptor oncogenesis. Trends Cell Biol 2009;19:542-551.
  38. Guo A, Villen J, Kornhauser J, et al. Signaling networks assembled by oncogenic EGFR and c-Met. Proc Natl Acad Sci USA 2008;105:692-697.
  39. Long IS, Han K, Li M, et al. Met receptor overexpression and oncogenic Ki-ras mutation cooperate to enhance tumorigenicity of colon cancer cells in vivo. Mol Cancer Res 2003;1:393-401.
  40. Ma PC, Kijima T, Maulik G, et al. C-MET mutational analysis in small cell lung cancer : novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res 2003;63:6272-6281
  41. Onitsuka T, Uramoto H, Ono K, et al. Comprehensive molecular analyses of lung adenocarcinoma with regard to the epidermal growth factor receptor, K-ras, MET and hepatocyte growth factor status. J Thorac Oncol 2010;5:591-596.
  42. Onozato R, Kosaka T, Kuwano H, Sekido Y, Yatabe Y, Mitsudomi T. Activation of MET by gene amplification or by splice mutations deleting the juxtamembrane domain in primaryresected lung cancers. J Thorac Oncol 2009;4:5-11.
  43. Cappuzzo F, Marchetti A, Skokan M, et al. Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancer patients. J Clin Oncol 2009;27:1667-1674.
  44. Kanteti R, Yala S, Ferguson MK, Salgia. MET, HGF, EGFR, and PXN gene copy number in lung cancer using DNA extracts from FFPE archival samples and prognostic significance. J Environ Pathol Toxicol Oncol 2009;28:89-98
  45. Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Sience 2007;316:1039-1043.
  46. Bean J, Brennan C, Shih JY, et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci USA 2007;104:20932-20937.
  47. Blumenschein GR Jr, Mills GB, Gonzalez-Angulo AM. Targeting the heptocyte growth factor-cMET axis in cancer therapy. J Clin Oncol 2012;30:3287-3296
  48. Oh D, Han S, Kim TM, et al. A phase I, open-label, nonrandomized trial of OPB-31121, a STAT3 inhibitor, in patients with advanced solid tumors. J Clin Oncol 2010;28 Suppl:Abstr e13056.
  49. Gonzalez de Castro D, Clarke PA, Al-Lazikani B, Workman P. Personalized cancer medicine: molecular diagnostics, predictive biomarkers, and drug resistance. Clin Pharmacol Ther 2013;93(3):252-9.
  50. -Blay JY. Personalized medicine in oncology: questions for the next 20 years, The Lancet Oncology 2012;13(5): 448-449.
  51. Cox D during the ProCaRT: BBMRI (Biobanking and BiomolecularResourcesResearch Infrastructure). National Research American Council:Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease, 2011.
  52. Clinical Lung Cancer Genome Project (CLCGP) and Network Genomic Medicine (NGM). A genomics-based classification of human lung tumors. SciTransl Med. 2013; 30:209ra153. doi: 10.1126/scitranslmed.3006802.
  53. Villaruz LC, Burns TF, Ramfidis VS, Socinski MA. Personalizing therapy in advanced non-small-cell lung cancer. SeminRespirCrit Care Med. 2013;34(6):822-36. doi: 10.1055/s-0033-1358552.