Polymer-drug conjugates as modulators of cellular apoptosis.

The successful clinical application of polymer-protein conjugates (PEGylated enzymes and cytokines) and the promising results arising from clinical trials with polymer-bound chemotherapy (eg, doxorubicin or paclitaxel) have established their potential to reduce toxicity and improve activity in chemotherapy-refractory patients. Furthermore, and more important, they have also provided a firm foundation for more sophisticated second-generation constructs that deliver the newly emerging target-directed bioactive agents (eg, modulators of apoptosis, cell cycle, anti-angiogenic drugs) in addition to polymer-based drug combinations (eg, endocrine therapy and chemotherapy). This review will focus on polymer-drug conjugate modulators of cellular apoptosis to be used as single pro-apoptotic (eg, cancer) or anti-apoptotic (eg, ischemia) agents or as a combination therapy.