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Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors.
Rolfo, Christian; Giovannetti, Elisa; Hong, David S; Bivona, T; Raez, Luis E; Bronte, Giuseppe; Buffoni, Lucio; Reguart, Noemí; Santos, Edgardo S; Germonpre, Paul; Taron, Mìquel; Passiglia, Francesco; Van Meerbeeck, Jan P; Russo, Antonio; Peeters, Marc; Gil-Bazo, Ignacio; Pauwels, Patrick; Rosell, Rafael.
Afiliação
  • Rolfo C; Phase I - Early Clinical Trials Unit, Oncology Department and Multidisciplinary Oncology Center Antwerp (MOCA) Antwerp University Hospital, Edegem, Belgium. Electronic address: christian.rolfo@uza.be.
  • Giovannetti E; Department Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
  • Hong DS; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Bivona T; Hematology and Oncology Department, Hellen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
  • Raez LE; Memorial Cancer Institute, Memorial Health Care System, Florida International University, Miami, FL, USA.
  • Bronte G; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
  • Buffoni L; San Giovanni Battista Molinette Hospital, Department of Medical Oncology, Turin, Italy.
  • Reguart N; Medical Oncology Department, Hospital Clinic, Barcelona, Spain.
  • Santos ES; Lynn Cancer Institute, Thoracic Oncology, Boca Raton, FL, USA.
  • Germonpre P; Department of Respiratory Medicine, AZ Maria Middelares, Kortrijksesteenweg 1026, 9000 Ghent, Belgium.
  • Taron M; Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
  • Passiglia F; Phase I - Early Clinical Trials Unit, Oncology Department and Multidisciplinary Oncology Center Antwerp (MOCA) Antwerp University Hospital, Edegem, Belgium; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
  • Van Meerbeeck JP; Thoracic Oncology, Multidisciplinary Oncology Center Antwerp (MOCA) Antwerp University Hospital, Edegem, Belgium.
  • Russo A; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
  • Peeters M; Department of Medical Oncology, University Hospital Antwerpen, Wilrijkstraat 10, 2650 Edegem, Belgium.
  • Gil-Bazo I; Department of Oncology, Clinica Universidad de Navarra, Pamplona, Spain.
  • Pauwels P; Molecular Pathology Unit, Pathology Department and Multidisciplinary Oncology Center Antwerp (MOCA) Antwerp University Hospital, Edegem, Belgium.
  • Rosell R; Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
Cancer Treat Rev ; 40(8): 990-1004, 2014 Sep.
Article em En | MEDLINE | ID: mdl-24953979
INTRODUCTION: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs. AREAS COVERED: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arise from secondary EGFR mutations. Other resistance-inducing processes include mesenchymal-epithelial transition factor (MET) amplification, epithelial-mesenchymal transformation, phenotypic change from NSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current therapeutic strategies to overcome these EGFR TKI resistance mechanisms focus on the inhibition or blocking of multiple members of the ErbB family. Several molecules which target multiple ErbB receptors are being investigated in NSCLC and other indications including afatinib, an ErbB Family Blocker, as well as dacomitinib and lapatinib. Novel, non-quinazoline, EGFR inhibitors, that also target EGFR activating and resistance (T790M) mutations, are currently under clinical development. Other therapeutic strategies include inhibition of parallel and downstream pathways, using agents which target heat shock protein (HSP)90 or poly (ADP-ribose) polymerase in addition to mammalian target of rapamycin (mTOR), monoclonal antibodies against the insulin-like growth factor-1 receptor, and fulvestrant-mediated oestrogen receptor regulation. CONCLUSION: Improved understanding of mechanisms underlying resistance to EGFR TKIs emphasises the importance of a genotype-guided approach to therapy. Elucidation of resistance mechanisms is indeed crucial to target innovative therapeutic approaches and to improve the efficacy of anticancer regimes in NSCLC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Inibidores de Proteínas Quinases / Receptores ErbB / Neoplasias Pulmonares Limite: Animals / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Inibidores de Proteínas Quinases / Receptores ErbB / Neoplasias Pulmonares Limite: Animals / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article