  Miniaturization is a hallmark of modern technologies. Notably, this feature
has not spared molecular biology and its potential applications. Towards
developing more effective therapeutics against cancer, studies began to explore
more than a decade ago how natural tumor suppression could be translated into
antineoplastic drugs. To this end, investigators focused on major constituents
of a central pathway that protects cells against neoplastic transformation: the
nuclear retinoblastoma protein (RB) pathway. As such, peptide mimetics of RB,
p16 and p21 were developed. Likewise, the p53 and von Hippel-Lindau gene
products which affect indirectly the RB pathway provided additional templates
for the development of anti-proliferative peptides. Each of the peptides
derived from these distinct tumor suppressors was made cell-permeable by its
ligation to an amino acid sequence conferring cellular internalization. Details
reviewed here reveal that through the application of such anti-cancer peptide
therapeutics alone or in conjunction whenever synergy is to expect, the dark
era of chemotherapy will likely be overcome, at last.
