Anti-tumor chemotherapy utilizing peptide-based approaches--apoptotic pathways, kinases, and proteasome as targets.
The pharmacological sciences are taking advantage of recent discoveries that have defined the molecular pathways governing apoptosis. These signaling cascades are frequently inactivated or distorted by mutations in cancer cells. Peptides derived from critical interaction, phosphorylation, or cleavage sites are the preferred leads (starting points) for the development of new drugs. In this review we summarize recent peptide-based approaches that target MDM2, p53, NF-kappaB, ErbB2, MAPK, as well as Smac/DIABLO, IAP BIR domains, and Bcl-2 interaction domains, with a specific focus on the BH3 domain. Separate parts of the review deal with proteasome inhibitors, integrin-derived peptides, and molecules that are being tested for tumor-selective delivery of anticancer drugs ("magic bullet" approach). The proteasome inhibitors and integrin-derived peptides show a variety of effects, targeting not only tumor growth, but also angiogenesis, metastasizing potential, and other cancer cell functions. The last part of this review describes approaches that use specific properties (surface receptors, increased enzymatic activities) of cancer cells in order to target them specifically. These new generations of anticancer drugs provide the foundations for therapies with fewer side effects and higher efficacy.
Mendoza
Francisco J
FJ
Manitoba Institute of Cell Biology, Cancer Care Manitoba, University of Manitoba, Winnipeg, MB R3E 0V9, Canada.
Espino
Paula S
PS
Cann
Kendra L
KL
Bristow
Nicolle
N
McCrea
Kristin
K
Los
Marek
M
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010455:Peptides / Q000627:therapeutic use*; D061988:Proteasome Inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010455:Peptides; D061988:Proteasome Inhibitors; D047428:Protein Kinase Inhibitors