Stayin' Alive

Science's STKE  24 Aug 2004:
Vol. 2004, Issue 247, pp. tw304
DOI: 10.1126/stke.2472004tw304

About 10% of patients with non-small cell lung cancer (NSCLC) experience dramatic tumor regression when treated with gefitinib (Iressa), a recently approved drug that inhibits the kinase activity of the epidermal growth factor receptor (EGFR). Tumors that respond to gefitinib harbor somatic mutations in the EGFR kinase domain. Sordella et al. now show that these mutant EGFRs activate a signaling pathway that keeps the tumor cells alive even when they are treated with agents that induce cell death, such as conventional chemotherapeutic drugs. The authors speculate that NSCLCs expressing the mutant EGFRs may become fully dependent on this cell survival pathway, which could explain, at least in part, their extreme sensitivity to gefitinib.

R. Sordella, D. W. Bell, D. A. Haber, J. Settleman, Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 305, 1163-1167 (2004). [Abstract] [Full Text]