Bleomycin: revival of an old drug

Abstract

1. Bleomycin (BLM) is a cytotoxic drug currently used in anticancer chemotherapy. We present here a summary of the well established "old" knowledge concerning BLM structure, properties and activity at the molecular level, as well as its current clinical uses. 2. Then, we introduce "new" recent facts concerning BLM interaction with animal cells, that demonstrate the peculiar characteristics of that drug and its potentialities. Indeed, BLM has an high intrinsic cytotoxicity (i.e. it is a very potent drug once inside the cell). However, BLM cytotoxicity is limited because BLM is unable to diffuse through the plasma membrane. The very low amounts of BLM that can reach the cell interior enter the cells by a mechanism that requires BLM interaction with a plasma membrane protein. 3. Finally, we present and discuss a new possible use of BLM in an antitumor approach that we term electrochemotherapy. This new treatment, still under development, is based on the increased BLM delivery into tumor cells after cell permeabilization by electric pulses administered locally at the solid tumor site. This results in a huge local potentiation of BLM activity, in the absence of systemic adverse effects. Clinical trials are in progress.