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Genetics

When two is worse than one

Nature Reviews Clinical Oncology volume 8, page 252 (2011)Cite this article

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Advanced non-small-cell lung carcinomas (NSCLC) that harbor mutations in EGFR represent the best example of oncogene-addicted tumors that respond to therapies designed to efficiently target the tumor's Achilles heel. In the past decade, tyrosine kinases inhibitors (TKIs) have increased the median progression-free survival (PFS) of patients with metastatic EGFR-mutant NSCLC by more than 14 months. However, primary and acquired resistance to such treatment puts a brake on the efficacy rates of these drugs and, unfortunately, not every patient shows the same promising response.

Rafael Rosell and colleagues were interested in identifying what determines the duration of these individual responses. Patients with EGFR-mutant tumors who develop acquired resistance to EGFR TKIs often develop a second-site mutation in the threonine residue at position 790, T790M. On this basis, the researchers examined the presence of this mutation in tumor samples of patients with NSCLC who had previously received erlotinib as first-line treatment and established a correlation with PFS. Of the 65 sequenced tumors, 21 had the T790M mutation. The PFS of these patients was 8 months compared with 18 months in those patients who did not harbor the mutation.

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ORIGINAL RESEARCH PAPER

  1. Rosell, R. et al. Pretreatment EGFR T790M mutation and BRCA1 mRNA expression in erlotinib-treated advanced non-small-cell lung cancer patients with EGFR mutations. Clin. Cancer Res. 17, 1160–1168 (2011)

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Authors
  1. M. Teresa Villanueva
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Villanueva, M. When two is worse than one. Nat Rev Clin Oncol 8, 252 (2011). https://doi.org/10.1038/nrclinonc.2011.48

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  • DOI: https://doi.org/10.1038/nrclinonc.2011.48

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