Approaches to Endow Ribonucleases with Antitumor Activity: Lessons Learned from the Native Cytotoxic Ribonucleases
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Typical antitumor drugs disrupt the flow of biochemical information from DNA to
proteins with the aim of precluding uncontrolled cell proliferation and inducing cancer
cell apoptosis. However, most of the currently used small antitumor drugs are genotoxic
because they act over DNA. Pharmaceutical industry is now searching for a new line of
cancer chemotherapeutics without genotoxic effectsǯ Ribonucleases (RNases) are small
basic proteins, present in all life forms, which belong to this kind of chemotherapeutics.
Some of them present with remarkable selective antitumor activity linked to their ability
to destroy RNA, a powerful way to control gene expression, leaving DNA unharmed.
In the last two decades, the knowledge gained on the cytotoxic mechanism of these
RNases has been used to engineer more powerful and selective variants to kill cancer
cells. In this chapter, we describe the advances reached in endowing an RNase with
antitumor abilities