Starving to succeed.

Cancer cells rely on the efficient and effective turnover of cell signaling molecules to ensure their continued survival, and hence depend on specific amino acids (AAs) for their growth and metastatic capabilities.  This dependence has been exploited by the recent, successful development of the proteasome inhibitor, bortezomib, which inhibits the degradation of proteins; and suggests that inhibitors of other essential steps in the mechanisms of cellular protein turnover may provide novel therapeutic targets.  The provision of free AAs within cancer cells is controlled by aminopeptidases which are responsible for the cleavage of AAs from the amino terminus of proteins or peptides.  Recent studies have demonstrated that the expression of aminopeptidases is upregulated in cancer cells compared to normal cells, providing a rationale for further study and development of clinical grade aminopeptidase inhibitors.