Growth and differentiation factors as cancer therapeutics

Differentiation therapy for the treatment of malignant disorders offers an attractive alternative to the conventional cytotoxic chemotherapy. The concept of differentiation therapy is based on the principal of 'reform' rather than 'retaliation'. The perception that malignant cell results from a block in the differentiation pathway has led to a conceptual strategy to remove this block and to re-establish normal homeostasis. Differentiation therapy, in general, is associated with a growth arrest and long-term commitment of the cell to die via apoptosis or senescence. The conventional cytotoxic therapy contrasts from the differentiation therapy in that there is no attempt to restore normal homeostasis in the former case and it is accompanied by immediate cell death. The treatment of acute pro-myelocytic leukemia (APL) by all-trans-retinoic acid (ATRA) revolutionized the treatment of the cancer and provided the first example and proof of concept of differentiation therapy. Therefore, the differentiation therapy may offer the opportunity for the use of the new, relatively non-toxic agents as well as the use of current chemotherapeutic agents at doses significantly lower than those maximally tolerated.