Targets cytotoxic agents

There are a number of reasons for expecting multi-targeted cancer therapy to be superior to targeted cancer therapy focused on a single target or to classical, nonselective cytotoxic agents. 

Doria, F. Richter, S.N. Nadai, M. Colloredo-Melz, S. Mella,M. Palumbo, M. Freccero, M. BINOL-amino acid conjugates as triggerable carriers of DNA-targeted potent photo-cytotoxic agents. J. Med. Chem. 2007, 50, 6570-6579. 

Platinum complexes are cytotoxic agents yet the paradigm in cancer chemotherapy has moved to a more targeted approach, with special emphasis on signaling pathways. In this respect a remarkable story is that of arsenic trioxide, As203 (Trisenox, Cell Therapeutics Inc, Seattle, USA) which was approved by the FDA in September 2000 for treatment of acute promomyelo-cytic leukemia (APL) in patients who have relapsed or are refractory to retinoid and anthracycline chemotherapy. An estimated 1,500 new cases of APL are diagnosed yearly in the US, of which an... 

Carboxypeptidase G2 (CPG2, glutamate carboxypeptidase, EC 3.4.17.11) is a bacterial enzyme not produced in mammalian cells. It has been used with promising success to target cytotoxic alkylating agents to tumor cells [60][61]. In a series of studies, a CPG2 monoclonal antibody con-... 

Of the non-antibody, non-liposome based drug targeting strategies, most of the (limited) clinical experience has been obtained with polymer-based conjugates of anticancer drugs. The most widely employed drugs for this application are cytotoxic agents such as doxorubicin and... 

The pharmacokinetic processing of macromolecules used as targeting devices or drug carrier systems is different from that of conventional cytotoxic drugs and plays an important role in e.g. the targeting efficiency of these cytotoxic agents coupled to the macromolecules. 

The major classes of immunosuppressive drugs employed in clinical practice to avoid tissue rejection include calcineurin inhibitors, target of rapamycin (TOR) inhibitors, sphingosine-1 -phosphate receptor (S1P-R) modulators, cytotoxic agents, glucocorticoids and monoclonal antibodies. These drugs need to be used on a lifelong basis and have major undesirable side effects. 

---