M Beau-Faller

Publications (7)24.66 Total impact

• Article: [A simple view on lung cancer biology: the MET pathway].

  A-M Ruppert, M Beau-Faller, L Belmont, A Lavolé, V Gounant, J Cadranel, M Wislez
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  ABSTRACT: MET is a cell membrane tyrosine kinase receptor for its ligand the hepatocyte growth factor (HGF), also called scatter factor (SF). MET conveys mitogenic, motogenic and proangiogenic signals, important during embryonic development and during the development of cancer. Activation of the HGF-MET pathway seems to be associated with a poor prognosis in lung cancer. Activation in lung cancer may be related to several molecular anomalies: ligand overexpression, receptor overexpression, genomic amplification or MET mutation. In MET amplified or mutated lung cancer, MET may be an important oncogene, as the tumor appears "MET addicted". In other lung cancers, MET may be implicated in tumour progression by tissue invasion and formation of metastases. MET amplification is also a mechanism known to be implicated in 20% of secondary resistance to EGFR inhibitors in patients presenting EGFR mutated lung cancer. Different strategies of MET inhibition in lung cancer are being studied, particularly in EGFR mutated lung cancer. In this review we discuss the structure of the MET receptor, the activated pathways, the main genomic anomalies in lung cancer and the development of MET inhibitors.
  Revue des Maladies Respiratoires 12/2011; 28(10):1241-9. · 0.59 Impact Factor
• Article: Immunohistochemistry to identify EGFR mutations or ALK rearrangements in patients with lung adenocarcinoma.

  P Hofman, M Ilie, V Hofman, S Roux, A Valent, A Bernheim, M Alifano, F Leroy-Ladurie, F Vaylet, I Rouquette, P Validire, M Beau-Faller, L Lacroix, J C Soria, P Fouret
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  ABSTRACT: Immunohistochemistry has been proposed as a specific and sensitive method to identify EGFR mutations or ALK rearrangements in lung tumours. We assessed EGFR and KRAS by direct sequencing in 154 patients with lung adenocarcinoma. ALK rearrangements were assayed by FISH and RT-PCR. Immunohistochemistry was carried out and evaluated closely following published methods using recommended monoclonal rabbit or mouse antibodies. Thirteen of 36 exon 19 EGFR-mutated tumours (36%)-including 12 of 22 with p.Glu746_Ala750del (55%)-were positive with the 6B6 antibody that was raised against p.Glu746_Ala750del. One hundred eleven of 114 EGFR exon 19 wild-type tumours (97%) were negative with 6B6. Four of 21 exon 21 EGFR-mutated tumours (19%)-including 4 of 17 with p.Leu858Arg (24%)-were positive with the 43B2 antibody that was raised against p.Leu858Arg. One hundred twenty-two of 124 (98%) EGFR exon 21 wild-type tumours were negative with 43B2. Two of four ALK rearrangements-including two of three with ELM4-ALK fusion transcripts-were identified with the 5A4 antibody. Eleven of 13 tumours without ALK rearrangement (85%) were negative with 5A4. Immunohistochemistry is a specific means for identification of EGFR mutations and ALK rearrangements. It suffers, however, from poor sensitivity.
  Annals of Oncology 11/2011; 23(7):1738-43. · 6.43 Impact Factor
• Article: EGFR-TKI and lung adenocarcinoma with CNS relapse: interest of molecular follow-up.

  A-M Ruppert, M Beau-Faller, A Neuville, E Guerin, A-C Voegeli, B Mennecier, M Legrain, A Molard, M-Y Jeung, M-P Gaub, P Oudet, E Quoix
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  ABSTRACT: The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) erlotinib improves survival of lung cancer as second- or third-line therapy. However, after an initial response, most patients will recur, particularly within the central nervous system. The present study reports the case of a 27-yr-old nonsmoking male presenting with a metastatic lung adenocarcinoma with EGFR exon 19 deletion, associated with sensitivity to EGFR-TKI. Gefitinib, followed by chemotherapy and finally erlotinib resulted in prolonged disease control, until multiple liver metastases were detected. After stopping EGFR-TKI, brain metastases with carcinomatous meningitis were diagnosed. A secondary T790M mutation, associated with resistance to EGFR-TKI, was found on the liver biopsy but not in the cerebrospinal fluid. Erlotinib was reintroduced and allowed a quick neurological improvement, even though the extra-cranial disease remained resistant to erlotinib. The present report underscores the interest of molecular monitoring in lung cancer. Persistent cerebral tyrosine kinase inhibitor sensitivity should be considered in patients presenting with an early central nervous system relapse after stopping epidermal growth factor receptor tyrosine kinase inhibitor, even with a T790M-resistant mutation in noncerebral metastases. Questions remain concerning the selection of sub-clones during epidermal growth factor receptor tyrosine kinase inhibitor therapy, which could differ according to metastatic sites, especially in the central nervous system.
  European Respiratory Journal 03/2009; 33(2):436-40. · 5.89 Impact Factor
• Source

  Available from: Elisabeth Quoix

  Article: Detection of K-Ras mutations in tumour samples of patients with non-small cell lung cancer using PNA-mediated PCR clamping.

  M Beau-Faller, M Legrain, A-C Voegeli, E Guérin, T Lavaux, A-M Ruppert, A Neuville, G Massard, J-M Wihlm, E Quoix, P Oudet, M P Gaub
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  ABSTRACT: Non-small cell lung cancers (NSCLC), in particular adenocarcinoma, are often mixed with normal cells. Therefore, low sensitivity of direct sequencing used for K-Ras mutation analysis could be inadequate in some cases. Our study focused on the possibility to increase the detection of K-Ras mutations in cases of low tumour cellularity. Besides direct sequencing, we used wild-type hybridisation probes and peptide-nucleic-acid (PNA)-mediated PCR clamping to detect mutations at codons 12 and 13, in 114 routine consecutive NSCLC frozen surgical tumours untreated by targeted drugs. The sensitivity of the analysis without or with PNA was 10 and 1% of tumour DNA, respectively. Direct sequencing revealed K-Ras mutations in 11 out of 114 tumours (10%). Using PNA-mediated PCR clamping, 10 additional cases of K-Ras mutations were detected (21 out of 114, 18%, P<0.005), among which five in samples with low tumour cellularity. In adenocarcinoma, K-Ras mutation frequency increased from 7 out of 55 (13%) by direct sequencing to 15 out of 55 (27%) by clamped-PCR (P<0.005). K-Ras mutations detected by these sensitive techniques lost its prognostic value. In conclusion, a rapid and sensitive PCR-clamping test avoiding macro or micro dissection could be proposed in routine analysis especially for NSCLC samples with low percentage of tumour cells such as bronchial biopsies or after neoadjuvant chemotherapy.
  British Journal of Cancer 03/2009; 100(6):985-92. · 5.04 Impact Factor
• Article: [In Process Citation]

  G Levallet, E Bergot, F Defraipont, C Creveuil, M Antoine, E Brambilla, M Beau-Faller, M Mounawar, Mc Favrot, P Hainaut, B Milleron, G Zalcman
  Revue des Maladies Respiratoires 12/2008; 25(9):1177. · 0.59 Impact Factor
• Article: [Targeted therapies in thoracic oncology].

  E Quoix, M Beau-Faller, J-Y Douillard, B Milleron
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  ABSTRACT: Better understanding of the alterations of cellular physiology during carcinogenesis has resulted in the development of new anticancer agents called biological targeted therapies. These therapies will probably complement the traditional treatments (surgery, radiotherapy and chemotherapy). In thoracic oncology, targeted therapies may interfere with signal transduction by interaction with growth factors receptors. This is the case with monoclonal antibodies directed against the extracellular part of the receptors and with small molecules inhibiting the intracellular part of the receptors (for example, EGF-R). Other strategies include the use of farnesyl transferase inhibitors or of antisense oligonucleotides; the new therapies may also inhibit angiogenesis by targeting either the VEGF receptor or the matrix metalloproteases. Inhibitors of metalloproteases were the first targeted agents tested. However, all published studies on metalloproteases inhibitors have been negative so far. Currently, the agents most advanced in clinical development are the EGFR inhibitors (either monoclonal antibodies or small molecules inhibiting tyrosine-kinases) which, in those that have clinical activity, may produce a sustained response at a cost of a degree of toxicity.
  Revue des Maladies Respiratoires 07/2004; 21(3 Pt 1):527-37. · 0.59 Impact Factor
• Article: Allelic imbalance at loci containing FGFR, FGF, c-Met and HGF candidate genes in non-small cell lung cancer sub-types, implication for progression.

  M Beau-Faller, M P Gaub, A Schneider, E Guérin, Nicolas Meyer, X Ducrocq, G Massard, B Gasser, R Kessler, E Weitzenblum, J M Wihlm, E Quoix, P Oudet
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  ABSTRACT: Fibroblast growth factors (FGF), hepatocyte growth factor (HGF) and their receptors, FGFR and c-Met, are essential components of the regulatory networks between the epithelium and mesenchyme in embryonic lung, but their respective roles in tumour growth are not clear. We performed allelotyping at loci containing the candidate genes FGFR-1-2-3-4, FGF-1-2-7-10, c-Met and HGF in 36 non-small cell lung cancer (NSCLC) (20 squamous-cell carcinomas (SQC) and 16 adenocarcinomas (ADC)), by surrounding each locus with two microsatellites (MS), as close as possible to the genes of interest. Unexpectedly, SQC and ADC were frequently altered at all of these loci, and SQC showed more simultaneously altered loci. In ADC, alterations at the 15q13-22 locus (FGF7 candidate gene) were significantly more frequent. Thus, these loci showed different patterns of molecular alterations between SQC and ADC. Finally, alterations at loci containing FGFR and HGF candidate genes were inversely correlated to the lymph node status in SQC and ADC, respectively.
  European Journal of Cancer 12/2003; 39(17):2538-47. · 5.54 Impact Factor