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01.08.2011 | Leitthema

Pathophysiologie und Molekulardiagnostik beim nichtkleinzelligen Lungenkarzinom

verfasst von: L.C. Heukamp, MB PhD, J. Wolf, R. Büttner

Erschienen in: Die Onkologie | Ausgabe 8/2011

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Zusammenfassung

Lungenkarzinome sind die häufigste tumorbedingte Todesursache in westlichen Industrienationen trotz kontinuierlicher Verbesserung der diagnostischen und therapeutischen Ansätze [1]. Vielversprechend ist die Entwicklung von zielgerichteten Substanzen („targeted drugs“) gegen onkogene Pathomechanismen des Bronchialkarzinoms („non-small cell lung cancer“, NSCLC). So kommen inzwischen Therapien zum Einsatz, die gegen den epidermalen Wachstumsfaktorrezeptor (EGFR) sowie gegen das transformierende EML4-ALK-Fusionsprotein („echinoderm microtubule-associated protein-like 4 gene“ und „anaplastic lymphoma kinase“) gerichtet sind. Diese Ansätze kommen jedoch fast nur Patienten zugute, die nie geraucht haben und relativ seltene Subtypen von Adenokarzinomen aufweisen. Gerichtete therapeutische Optionen für die häufigen Plattenepithelkarzinome bei Rauchern gibt es bisher noch nicht. Kürzlich jedoch wurden Amplifikationen des Fibroblastenwachstumsfaktorrezeptor-Typ-1(FGFR1)-Gens als mögliche therapeutische Zielstruktur in dieser Patientengruppe identifiziert und finden gerade den Weg in erste klinische Studien. Der folgende Beitrag gibt eine Übersicht über die Pathomechanismen und die Molekulardiagnostik des Lungenkarzinoms zur Therapiestratifizierung.
Literatur
2.
Zurück zum Zitat Sobol RE et al (1987) Epidermal growth factor receptor expression in human lung carcinomas defined by a monoclonal antibody. J Natl Cancer Inst 79(3):403–407PubMed Sobol RE et al (1987) Epidermal growth factor receptor expression in human lung carcinomas defined by a monoclonal antibody. J Natl Cancer Inst 79(3):403–407PubMed
3.
Zurück zum Zitat Ciardiello F, Tortora G (2001) A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res 7(10):2958–2970PubMed Ciardiello F, Tortora G (2001) A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res 7(10):2958–2970PubMed
4.
Zurück zum Zitat Mok TS et al (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361(10):947–957PubMedCrossRef Mok TS et al (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361(10):947–957PubMedCrossRef
5.
Zurück zum Zitat Lynch TJ et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350(21):2129–2139PubMedCrossRef Lynch TJ et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350(21):2129–2139PubMedCrossRef
6.
Zurück zum Zitat Paez JG et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304(5676):1497–1500PubMedCrossRef Paez JG et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304(5676):1497–1500PubMedCrossRef
7.
Zurück zum Zitat Riely GJ et al (2006) Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib. Clin Cancer Res 12(3 Pt 1):839–844PubMedCrossRef Riely GJ et al (2006) Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib. Clin Cancer Res 12(3 Pt 1):839–844PubMedCrossRef
8.
Zurück zum Zitat Humphrey PA et al (1988) Amplification and expression of the epidermal growth factor receptor gene in human glioma xenografts. Cancer Res 48(8):2231–2238PubMed Humphrey PA et al (1988) Amplification and expression of the epidermal growth factor receptor gene in human glioma xenografts. Cancer Res 48(8):2231–2238PubMed
9.
Zurück zum Zitat Yamazaki H et al (1988) Amplification of the structurally and functionally altered epidermal growth factor receptor gene (c-erbB) in human brain tumors. Mol Cell Biol 8(4):1816–1820PubMed Yamazaki H et al (1988) Amplification of the structurally and functionally altered epidermal growth factor receptor gene (c-erbB) in human brain tumors. Mol Cell Biol 8(4):1816–1820PubMed
10.
Zurück zum Zitat Malden LT et al (1988) Selective amplification of the cytoplasmic domain of the epidermal growth factor receptor gene in glioblastoma multiforme. Cancer Res 48(10):2711–2714PubMed Malden LT et al (1988) Selective amplification of the cytoplasmic domain of the epidermal growth factor receptor gene in glioblastoma multiforme. Cancer Res 48(10):2711–2714PubMed
11.
Zurück zum Zitat Kwatra MM, Bigner DD, Cohn JA (1992) The ligand binding domain of the epidermal growth factor receptor is not required for receptor dimerization. Biochim Biophys Acta 1134(2):178–181PubMedCrossRef Kwatra MM, Bigner DD, Cohn JA (1992) The ligand binding domain of the epidermal growth factor receptor is not required for receptor dimerization. Biochim Biophys Acta 1134(2):178–181PubMedCrossRef
12.
Zurück zum Zitat Chattopadhyay A et al (1999) The role of individual SH2 domains in mediating association of phospholipase C-gamma1 with the activated EGF receptor. J Biol Chem 274(37):26091–26097PubMedCrossRef Chattopadhyay A et al (1999) The role of individual SH2 domains in mediating association of phospholipase C-gamma1 with the activated EGF receptor. J Biol Chem 274(37):26091–26097PubMedCrossRef
13.
Zurück zum Zitat Batzer AG et al (1994) Hierarchy of binding sites for Grb2 and Shc on the epidermal growth factor receptor. Mol Cell Biol 14(8):5192–5201PubMed Batzer AG et al (1994) Hierarchy of binding sites for Grb2 and Shc on the epidermal growth factor receptor. Mol Cell Biol 14(8):5192–5201PubMed
14.
Zurück zum Zitat Johnson GL, Vaillancourt RR (1994) Sequential protein kinase reactions controlling cell growth and differentiation. Curr Opin Cell Biol 6(2):230–238PubMedCrossRef Johnson GL, Vaillancourt RR (1994) Sequential protein kinase reactions controlling cell growth and differentiation. Curr Opin Cell Biol 6(2):230–238PubMedCrossRef
15.
Zurück zum Zitat Alvarez JV et al (2006) Signal transducer and activator of transcription 3 is required for the oncogenic effects of non-small-cell lung cancer-associated mutations of the epidermal growth factor receptor. Cancer Res 66(6):3162–3168PubMedCrossRef Alvarez JV et al (2006) Signal transducer and activator of transcription 3 is required for the oncogenic effects of non-small-cell lung cancer-associated mutations of the epidermal growth factor receptor. Cancer Res 66(6):3162–3168PubMedCrossRef
16.
Zurück zum Zitat Jorissen RN et al (2003) Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res 284(1):31–53PubMedCrossRef Jorissen RN et al (2003) Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res 284(1):31–53PubMedCrossRef
17.
Zurück zum Zitat Stoscheck CM, King LE Jr (1986) Role of epidermal growth factor in carcinogenesis. Cancer Res 46(3):1030–1037PubMed Stoscheck CM, King LE Jr (1986) Role of epidermal growth factor in carcinogenesis. Cancer Res 46(3):1030–1037PubMed
18.
Zurück zum Zitat Woodburn JR (1999) The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol Ther 82(2–3):241–250 Woodburn JR (1999) The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol Ther 82(2–3):241–250
19.
Zurück zum Zitat Sung T et al (2000) Preferential inactivation of the p53 tumor suppressor pathway and lack of EGFR amplification distinguish de novo high grade pediatric astrocytomas from de novo adult astrocytomas. Brain Pathol 10(2):249–259PubMedCrossRef Sung T et al (2000) Preferential inactivation of the p53 tumor suppressor pathway and lack of EGFR amplification distinguish de novo high grade pediatric astrocytomas from de novo adult astrocytomas. Brain Pathol 10(2):249–259PubMedCrossRef
20.
Zurück zum Zitat Salomon DS et al (1995) Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 19(3):183–232PubMedCrossRef Salomon DS et al (1995) Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 19(3):183–232PubMedCrossRef
21.
Zurück zum Zitat Porebska I, Harlozinska A, Bojarowski T (2000) Expression of the tyrosine kinase activity growth factor receptors (EGFR, ERB B2, ERB B3) in colorectal adenocarcinomas and adenomas. Tumur Biol 21(2):105–115CrossRef Porebska I, Harlozinska A, Bojarowski T (2000) Expression of the tyrosine kinase activity growth factor receptors (EGFR, ERB B2, ERB B3) in colorectal adenocarcinomas and adenomas. Tumur Biol 21(2):105–115CrossRef
22.
Zurück zum Zitat Hynes NE, Lane HA (2005) ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 5(5):341–354PubMedCrossRef Hynes NE, Lane HA (2005) ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 5(5):341–354PubMedCrossRef
23.
Zurück zum Zitat Normanno N et al (2003) Target-based agents against ErbB receptors and their ligands: a novel approach to cancer treatment. Endocr Relat Cancer 10(1):1–21PubMedCrossRef Normanno N et al (2003) Target-based agents against ErbB receptors and their ligands: a novel approach to cancer treatment. Endocr Relat Cancer 10(1):1–21PubMedCrossRef
24.
Zurück zum Zitat Grunwald V, Hidalgo M (2003) Developing inhibitors of the epidermal growth factor receptor for cancer treatment. J Natl Cancer Inst 95(12):851–867PubMedCrossRef Grunwald V, Hidalgo M (2003) Developing inhibitors of the epidermal growth factor receptor for cancer treatment. J Natl Cancer Inst 95(12):851–867PubMedCrossRef
25.
Zurück zum Zitat Mendelsohn J, Baselga J (2003) Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 21(14):2787–2799PubMedCrossRef Mendelsohn J, Baselga J (2003) Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 21(14):2787–2799PubMedCrossRef
26.
Zurück zum Zitat Masui H et al (1984) Growth inhibition of human tumor cells in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies. Cancer Res 44(3):1002–1007PubMed Masui H et al (1984) Growth inhibition of human tumor cells in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies. Cancer Res 44(3):1002–1007PubMed
27.
Zurück zum Zitat Li S et al (2005) Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell 7(4):301–311PubMedCrossRef Li S et al (2005) Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell 7(4):301–311PubMedCrossRef
28.
Zurück zum Zitat Galizia G et al (2007) Cetuximab, a chimeric human mouse anti-epidermal growth factor receptor monoclonal antibody, in the treatment of human colorectal cancer. Oncogene 26(25):3654–3660PubMedCrossRef Galizia G et al (2007) Cetuximab, a chimeric human mouse anti-epidermal growth factor receptor monoclonal antibody, in the treatment of human colorectal cancer. Oncogene 26(25):3654–3660PubMedCrossRef
29.
Zurück zum Zitat Saltz LRM, Hochster H et al (2001) Cetuximab (IMC-C225) plus irinotecan (CPT-11) is active in CPT-11-refractory colorectal cancer (CRC) that expresses epidermal growth factor receptor (EGFR). Proc Am Soc Clin Oncol 20:3a (abstr 7) Saltz LRM, Hochster H et al (2001) Cetuximab (IMC-C225) plus irinotecan (CPT-11) is active in CPT-11-refractory colorectal cancer (CRC) that expresses epidermal growth factor receptor (EGFR). Proc Am Soc Clin Oncol 20:3a (abstr 7)
30.
Zurück zum Zitat Moroni M et al (2005) Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol 6(5):279–286PubMedCrossRef Moroni M et al (2005) Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol 6(5):279–286PubMedCrossRef
31.
Zurück zum Zitat Perez-Soler R et al (2004) Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer. J Clin Oncol 22(16):3238–3247PubMedCrossRef Perez-Soler R et al (2004) Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer. J Clin Oncol 22(16):3238–3247PubMedCrossRef
32.
Zurück zum Zitat Pao W et al (2004) 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 U S A 101(36):13306–13311PubMedCrossRef Pao W et al (2004) 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 U S A 101(36):13306–13311PubMedCrossRef
33.
Zurück zum Zitat Yang CH et al (2008) Specific EGFR mutations predict treatment outcome of stage IIIB/IV patients with chemotherapy-naive non-small-cell lung cancer receiving first-line gefitinib monotherapy. J Clin Oncol 26(16):2745–2753PubMedCrossRef Yang CH et al (2008) Specific EGFR mutations predict treatment outcome of stage IIIB/IV patients with chemotherapy-naive non-small-cell lung cancer receiving first-line gefitinib monotherapy. J Clin Oncol 26(16):2745–2753PubMedCrossRef
34.
Zurück zum Zitat Bunn PA Jr et al (2006) Biological markers for non-small cell lung cancer patient selection for epidermal growth factor receptor tyrosine kinase inhibitor therapy. Clin Cancer Res 12(12):3652–3656PubMedCrossRef Bunn PA Jr et al (2006) Biological markers for non-small cell lung cancer patient selection for epidermal growth factor receptor tyrosine kinase inhibitor therapy. Clin Cancer Res 12(12):3652–3656PubMedCrossRef
35.
Zurück zum Zitat Li AR et al (2008) EGFR mutations in lung adenocarcinomas: clinical testing experience and relationship to EGFR gene copy number and immunohistochemical expression. J Mol Diagn 10(3):242–248PubMedCrossRef Li AR et al (2008) EGFR mutations in lung adenocarcinomas: clinical testing experience and relationship to EGFR gene copy number and immunohistochemical expression. J Mol Diagn 10(3):242–248PubMedCrossRef
36.
Zurück zum Zitat Rosell R et al (2009) Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 361(10):958–967PubMedCrossRef Rosell R et al (2009) Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 361(10):958–967PubMedCrossRef
37.
Zurück zum Zitat Marchetti A et al (2009) Clinical implications of KRAS mutations in lung cancer patients treated with tyrosine kinase inhibitors: an important role for mutations in minor clones. Neoplasia 11(10):1084–1092PubMed Marchetti A et al (2009) Clinical implications of KRAS mutations in lung cancer patients treated with tyrosine kinase inhibitors: an important role for mutations in minor clones. Neoplasia 11(10):1084–1092PubMed
38.
Zurück zum Zitat Rodenhuis S et al (1988) Incidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung. Cancer Res 48(20):5738–5741PubMed Rodenhuis S et al (1988) Incidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung. Cancer Res 48(20):5738–5741PubMed
39.
Zurück zum Zitat Ahrendt SA et al (2001) Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung. Cancer 92(6):1525–1530PubMedCrossRef Ahrendt SA et al (2001) Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung. Cancer 92(6):1525–1530PubMedCrossRef
40.
Zurück zum Zitat Pao W et al (2005) KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2(1):e17PubMedCrossRef Pao W et al (2005) KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2(1):e17PubMedCrossRef
41.
Zurück zum Zitat Pao W et al (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2(3):e73PubMedCrossRef Pao W et al (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2(3):e73PubMedCrossRef
42.
Zurück zum Zitat Han SW et al (2006) Optimization of patient selection for gefitinib in non-small cell lung cancer by combined analysis of epidermal growth factor receptor mutation, K-ras mutation, and Akt phosphorylation. Clin Cancer Res 12(8):2538–2544PubMedCrossRef Han SW et al (2006) Optimization of patient selection for gefitinib in non-small cell lung cancer by combined analysis of epidermal growth factor receptor mutation, K-ras mutation, and Akt phosphorylation. Clin Cancer Res 12(8):2538–2544PubMedCrossRef
43.
Zurück zum Zitat Lievre A et al (2006) KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 66(8):3992–3995PubMedCrossRef Lievre A et al (2006) KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 66(8):3992–3995PubMedCrossRef
44.
Zurück zum Zitat Benvenuti S et al (2007) Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 67(6):2643–2648PubMedCrossRef Benvenuti S et al (2007) Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 67(6):2643–2648PubMedCrossRef
45.
Zurück zum Zitat Khambata-Ford S et al (2007) Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 25(22):3230–3237PubMedCrossRef Khambata-Ford S et al (2007) Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 25(22):3230–3237PubMedCrossRef
46.
Zurück zum Zitat Massarelli E et al (2007) KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. Clin Cancer Res 13(10):2890–2896PubMedCrossRef Massarelli E et al (2007) KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. Clin Cancer Res 13(10):2890–2896PubMedCrossRef
47.
Zurück zum Zitat Tsao MZC, Sakurada A et al (2006) An analysis of the prognostic and predictive importance of K-ras mutation status in the National Cancer Institute of Canada Clinical Trials Group BR.21 study of erlotinib versus placebo in the treatment of non-small cell lung cancer. J Clin Oncol (24):365s Tsao MZC, Sakurada A et al (2006) An analysis of the prognostic and predictive importance of K-ras mutation status in the National Cancer Institute of Canada Clinical Trials Group BR.21 study of erlotinib versus placebo in the treatment of non-small cell lung cancer. J Clin Oncol (24):365s
48.
Zurück zum Zitat Eberhard DA et al (2005) Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 23(25):5900–5909PubMedCrossRef Eberhard DA et al (2005) Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 23(25):5900–5909PubMedCrossRef
49.
Zurück zum Zitat De Roock W et al (2008) KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 19(3):508–515 De Roock W et al (2008) KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 19(3):508–515
50.
Zurück zum Zitat Yousem SA, Nikiforova M, Nikiforov Y (2008) The histopathology of BRAF-V600E-mutated lung adenocarcinoma. Am J Surg Pathol 32(9):1317–1321PubMedCrossRef Yousem SA, Nikiforova M, Nikiforov Y (2008) The histopathology of BRAF-V600E-mutated lung adenocarcinoma. Am J Surg Pathol 32(9):1317–1321PubMedCrossRef
51.
Zurück zum Zitat Yamamoto H et al (2008) PIK3CA mutations and copy number gains in human lung cancers. Cancer Res 68(17):6913–6921PubMedCrossRef Yamamoto H et al (2008) PIK3CA mutations and copy number gains in human lung cancers. Cancer Res 68(17):6913–6921PubMedCrossRef
52.
Zurück zum Zitat Gandhi J et al (2009) Alterations in genes of the EGFR signaling pathway and their relationship to EGFR tyrosine kinase inhibitor sensitivity in lung cancer cell lines. PLoS ONE 4(2):e4576PubMedCrossRef Gandhi J et al (2009) Alterations in genes of the EGFR signaling pathway and their relationship to EGFR tyrosine kinase inhibitor sensitivity in lung cancer cell lines. PLoS ONE 4(2):e4576PubMedCrossRef
53.
Zurück zum Zitat Lin E et al (2009) Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers. Mol Cancer Res 7(9):1466–1476PubMedCrossRef Lin E et al (2009) Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers. Mol Cancer Res 7(9):1466–1476PubMedCrossRef
54.
Zurück zum Zitat Shaw AT et al (2009) Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol 27(26):4247–4253PubMedCrossRef Shaw AT et al (2009) Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol 27(26):4247–4253PubMedCrossRef
55.
Zurück zum Zitat Yi ES et al (2011) Correlation of IHC and FISH for ALK gene rearrangement in non-small cell lung carcinoma: IHC score algorithm for FISH. J Thorac Oncol 6(3):459–465PubMedCrossRef Yi ES et al (2011) Correlation of IHC and FISH for ALK gene rearrangement in non-small cell lung carcinoma: IHC score algorithm for FISH. J Thorac Oncol 6(3):459–465PubMedCrossRef
56.
Zurück zum Zitat Paik JH et al (2011) Screening of anaplastic lymphoma kinase rearrangement by immunohistochemistry in non-small cell lung cancer: correlation with fluorescence in situ hybridization. J Thorac Oncol 6(3):466–472PubMedCrossRef Paik JH et al (2011) Screening of anaplastic lymphoma kinase rearrangement by immunohistochemistry in non-small cell lung cancer: correlation with fluorescence in situ hybridization. J Thorac Oncol 6(3):466–472PubMedCrossRef
57.
Zurück zum Zitat Horn L, Pao W (2009) EML4-ALK: honing in on a new target in non-small-cell lung cancer. J Clin Oncol 27(26):4232–4235PubMedCrossRef Horn L, Pao W (2009) EML4-ALK: honing in on a new target in non-small-cell lung cancer. J Clin Oncol 27(26):4232–4235PubMedCrossRef
58.
Zurück zum Zitat Kobayashi S et al (2005) EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 352(8):786–792PubMedCrossRef Kobayashi S et al (2005) EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 352(8):786–792PubMedCrossRef
59.
Zurück zum Zitat Sharma SV et al (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 7(3):169–181PubMedCrossRef Sharma SV et al (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 7(3):169–181PubMedCrossRef
60.
Zurück zum Zitat Kumar A et al (2008) Structure and clinical relevance of the epidermal growth factor receptor in human cancer. J Clin Oncol 26(10):1742–1751PubMedCrossRef Kumar A et al (2008) Structure and clinical relevance of the epidermal growth factor receptor in human cancer. J Clin Oncol 26(10):1742–1751PubMedCrossRef
61.
Zurück zum Zitat Yun CH et al (2007) Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell 11(3):217–227PubMedCrossRef Yun CH et al (2007) Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell 11(3):217–227PubMedCrossRef
62.
Zurück zum Zitat Maheswaran S et al (2008) Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 359(4):366–377PubMedCrossRef Maheswaran S et al (2008) Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 359(4):366–377PubMedCrossRef
63.
Zurück zum Zitat Miller VA et al (2010) Phase IIb/III double-blind randomized trial of BIBW 2992, an irreversible inhibitor of EGFR/HER1 and HER2 + best supportive care (BSC) versus placebo + BSC in patients with NSCLC failing 1–2 lines of chemotherapy and erlotinib or gefitinib (LUX-Lung1). Annual Meeting Europ Soc Med Oncol (ESMO), Milan, October 2010. Abstract ID: LBA1 Miller VA et al (2010) Phase IIb/III double-blind randomized trial of BIBW 2992, an irreversible inhibitor of EGFR/HER1 and HER2 + best supportive care (BSC) versus placebo + BSC in patients with NSCLC failing 1–2 lines of chemotherapy and erlotinib or gefitinib (LUX-Lung1). Annual Meeting Europ Soc Med Oncol (ESMO), Milan, October 2010. Abstract ID: LBA1
64.
Zurück zum Zitat Regales L et al (2009) Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer. J Clin Invest 119(10):3000–3010PubMed Regales L et al (2009) Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer. J Clin Invest 119(10):3000–3010PubMed
65.
Zurück zum Zitat Sos ML et al (2009) PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR. Cancer Res 69(8):3256–3261PubMedCrossRef Sos ML et al (2009) PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR. Cancer Res 69(8):3256–3261PubMedCrossRef
66.
Zurück zum Zitat Engelman JA et al (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316(5827):1039–1043PubMedCrossRef Engelman JA et al (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316(5827):1039–1043PubMedCrossRef
67.
Zurück zum Zitat Di Nicolantonio F et al (2008) Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 26(35):5705–5712CrossRef Di Nicolantonio F et al (2008) Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 26(35):5705–5712CrossRef
68.
Zurück zum Zitat Balak MN et al (2006) Novel D761Y and common secondary T790 M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res 12(21):6494–6501PubMedCrossRef Balak MN et al (2006) Novel D761Y and common secondary T790 M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res 12(21):6494–6501PubMedCrossRef
69.
Zurück zum Zitat Weiss J et al (2010) Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Translat Med 2(62):62ra93CrossRef Weiss J et al (2010) Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Translat Med 2(62):62ra93CrossRef
70.
Zurück zum Zitat Penzel R et al (2010) EGFR mutation detection in NSCLC-assessment of diagnostic application and recommendations of the German Panel for Mutation Testing in NSCLC. Virchows Arch 458(1):95–98PubMedCrossRef Penzel R et al (2010) EGFR mutation detection in NSCLC-assessment of diagnostic application and recommendations of the German Panel for Mutation Testing in NSCLC. Virchows Arch 458(1):95–98PubMedCrossRef
Metadaten
Titel
Pathophysiologie und Molekulardiagnostik beim nichtkleinzelligen Lungenkarzinom
verfasst von
L.C. Heukamp, MB PhD
J. Wolf
R. Büttner
Publikationsdatum
01.08.2011
Verlag
Springer-Verlag
Erschienen in
Die Onkologie / Ausgabe 8/2011
Print ISSN: 2731-7226
Elektronische ISSN: 2731-7234
DOI
https://doi.org/10.1007/s00761-011-2032-x

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Endometriose-Subtypen und das Risiko für Ovarialkarzinome

19.07.2024 Ovarialkarzinom Nachrichten

US-Kohortendaten sprechen dafür, dass verschiedene Endometrioseformen unterschiedlich mit dem Risiko für Ovarialkarzinome assoziiert sind. Besonders erhöht ist das Risiko offenbar bei tief infiltrierenden und ovariellen Endometrioseformen.

Die zelluläre Differenzierung wird wiederhergestellt

18.07.2024 Akute myeloische Leukämie Nachrichten

Ivosidenib von Servier ist ein Inhibitor der mutierten Isoform der Isocitrat-Dehydrogenase-1 (IDH1) und wird zur Behandlung von Patientinnen und Patienten mit neu diagnostizierter akuter myeloischer Leukämie (AML) eingesetzt. Die Substanz sorgt für die Wiederherstellung der zellulären Differenzierung.

Weißer Hautkrebs: Ein Update zu Diagnostik und Therapie

18.07.2024 Fortbildungswoche 2024 Kongressbericht

In der aktualisierten Version der S3-Leitlinie „Aktinische Keratose und Plattenepithelkarzinom der Haut“ gibt es neue Empfehlungen, unter anderem zu erweiterten Optionen bei aktinischer Keratose sowie zur systemischen und chirurgischen Behandlung von Plattenepithelkarzinomen. Ein Überblick.

Update Onkologie

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