Proteasome inhibition in small-cell lung cancer: preclinical rationale and clinical applications.

Primo N Lara, Richard J Bold, Philip Mack, Angela M. Davies, Paul H. Gumerlock, David R Gandara

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Abstract

Small-cell lung cancer (SCLC) is a tobacco-related malignancy that usually presents in an extensive and therefore incurable stage. Although initially sensitive to platinum agent-based therapy, SCLC rapidly becomes refractory to chemotherapy, leading to disease recurrence and ultimately patient death. Treatment options following failure of first-line platinum agent-based therapy are limited. Small-cell lung cancer is characterized by molecular aberrancies such as overexpression of the antiapoptotic protein Bcl-2, which is regulated in part by the inhibitory IkappaB, a target of the ubiquitin-proteasome degradative pathway. Bortezomib is a proteasome inhibitor that can decrease Bcl-2 expression through diminished IkappaB degradation. Efforts to promote apoptosis in SCLC through the integration of bortezomib into therapy are under way.

Original languageEnglish (US)
JournalClinical lung cancer.
Volume7 Suppl 2
StatePublished - Oct 2005

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ASJC Scopus subject areas

  • Cancer Research
  • Pulmonary and Respiratory Medicine

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