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Epidermal growth factor receptor (EGFR) mutations in lung cancer: preclinical and clinical data
Jorge, S.E.D.C.; Kobayashi, S.S.; Costa, D.B..
  • Jorge, S.E.D.C.; Harvard Medical School. Beth Israel Deaconess Medical Center. Department of Medicine. Division of Hematology/Oncology. Boston. US
  • Kobayashi, S.S.; Harvard Medical School. Beth Israel Deaconess Medical Center. Department of Medicine. Division of Hematology/Oncology. Boston. US
  • Costa, D.B.; Harvard Medical School. Beth Israel Deaconess Medical Center. Department of Medicine. Division of Hematology/Oncology. Boston. US
Braz. j. med. biol. res ; 47(11): 929-939, 11/2014. tab, graf
Article in English | LILACS | ID: lil-723897
ABSTRACT
Lung cancer leads cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC), the most prevalent subtype of this recalcitrant cancer, is usually diagnosed at advanced stages, and available systemic therapies are mostly palliative. The probing of the NSCLC kinome has identified numerous nonoverlapping driver genomic events, including epidermal growth factor receptor (EGFR) gene mutations. This review provides a synopsis of preclinical and clinical data on EGFR mutated NSCLC and EGFR tyrosine kinase inhibitors (TKIs). Classic somatic EGFR kinase domain mutations (such as L858R and exon 19 deletions) make tumors addicted to their signaling cascades and generate a therapeutic window for the use of ATP-mimetic EGFR TKIs. The latter inhibit these kinases and their downstream effectors, and induce apoptosis in preclinical models. The aforementioned EGFR mutations are stout predictors of response and augmentation of progression-free survival when gefitinib, erlotinib, and afatinib are used for patients with advanced NSCLC. The benefits associated with these EGFR TKIs are limited by the mechanisms of tumor resistance, such as the gatekeeper EGFR-T790M mutation, and bypass activation of signaling cascades. Ongoing preclinical efforts for treating resistance have started to translate into patient care (including clinical trials of the covalent EGFR-T790M TKIs AZD9291 and CO-1686) and hold promise to further boost the median survival of patients with EGFR mutated NSCLC.
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Full text: Available Index: LILACS (Americas) Main subject: Protein-Tyrosine Kinases / Carcinoma, Non-Small-Cell Lung / ErbB Receptors / Lung Neoplasms / Mutation Type of study: Prognostic study Limits: Humans Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2014 Type: Article / Project document Affiliation country: United States Institution/Affiliation country: Harvard Medical School/US

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Full text: Available Index: LILACS (Americas) Main subject: Protein-Tyrosine Kinases / Carcinoma, Non-Small-Cell Lung / ErbB Receptors / Lung Neoplasms / Mutation Type of study: Prognostic study Limits: Humans Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2014 Type: Article / Project document Affiliation country: United States Institution/Affiliation country: Harvard Medical School/US