title: Overcoming resistance to first/second generation epidermal growth factor receptor tyrosine kinase inhibitors and ALK inhibitors in oncogene-addicted advanced non-small cell lung cancer.
abstract: Epidermal growth factor receptor (EGFR) activating mutations and anaplastic lymphoma kinase (ALK) gene rearrangement in advanced non-small cell lung cancer (NSCLC) represent the two oncogenic events with an impact on current clinical practice. EGFR tyrosine kinase inhibitors (TKIs) and crizotinib are the standard of care for the treatment of EGFR mutant and ALK gene rearranged advanced NSCLC patients. Unfortunately, despite initial clinical benefit, acquired resistance to EGFR-TKIs or crizotinib usually develops after an average of 10-12 months of treatment. The aim of this review is to describe the mechanisms of resistance to first/second generation EGFR-TKIs and crizotinib. In particular, we focus on strategies to overcome resistance due to secondary EGFR T790M mutation and mutations of the ALK domain.
authors.affiliation: Cancer Research UK Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK, and Medical Oncology Unit, Papageorgiou General Hospital, Thessaloniki, Greece.
authors.forename: Ourania
authors.initials: O
authors.lastname: Romanidou
authors.affiliation: Department of Medical Oncology, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Landi
authors.affiliation: Department of Medical Oncology, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Federico
authors.initials: F
authors.lastname: Cappuzzo
authors.affiliation: Cancer Research UK Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Califano
keywords: AZD9291; EGFR-TKIs; EML-ALK gene rearrangement; ceritinib; crizotinib; epidermal growth factor receptor mutations; resistance; rociletinib