Fast, hungry and unstable: finding the Achilles' heel of small-cell lung cancer

Abstract

Over 95% of patients with small-cell lung cancer (SCLC) die within five years of diagnosis. The standard of care and the dismal prognosis for this disease have not changed significantly over the past 25 years. Some of the characteristics of SCLC that have defined it as a particularly virulent form of cancer -- rapid proliferation, excessive metabolic and angiogenic dependence, apoptotic imbalance and genetic instability -- are now being pursued as tumor-specific targets for intervention both in preclinical and early phase clinical studies. Here, we summarize areas of ongoing anti-cancer drug development, including classes of agents that target essential pathways regulating proliferation, angiogenesis, apoptotic resistance, chromosomal and protein stability, and cell-cell and cell-matrix interaction.

Figure 1

Diverse cellular processes that contribute to malignant transformation are being targeted through the development of new therapeutics for SCLC. Key components of proliferative signaling pathways are shown here, including tumor-associated angiogenesis, cell-survival pathways, mediators of chromosomal stability and replication, protein folding and stability, and cell–cell and cell–matrix interactions.