Modular protein engineering in emerging cancer therapies

An urgent need of more effective and personalized treatments for cancer and other genetic diseases is becoming a generalized claim. This is pushing forward experimental alternative approaches based on targeted nanoconjugates, which are designed to be specifically directed against target cells. These constructs, although suitable to carry conventional chemical drugs, are specifically appropriate to deliver expressible or antisense DNA molecules, silencing RNAs or functional proteins as novel biopharmaceuticals. In this new scenario, the specificity and adequateness of director moieties to target cells is fundamental to achieve successful therapies. In this regard, natural or modified proteins or short peptides offer appropriate tools to functionalize vehicles for targeted drug delivery. Besides, conventional protein engineering allows combining, by recombinant DNA technologies, different active peptides in single-chain polypeptides with modular architecture. This offers intriguing possibilities for the development of multifunctional and smart drug vehicles at the nanoscale. In this review we first discuss the pharmacological applications of recombinant proteins, the procedures to identify, obtain and engineer functional and multifunctional polypeptides for target drug delivery and the potential applications of such constructs in emerging cancer therapies. For that, we discuss in detail the molecular traits in the biology of cancer that are critical for the identification and selection of suitable targets for protein-based drug delivery. © 2009 Bentham Science Publishers Ltd.