Target-specific cancer treatment: chronic granulocytic leukemia as a model

Abstract

Cancer causes major morbidity and mortality worldwide. Modest therapeutic success attends the use of non-selective chemotherapy and irradiation. However, injury to normal tissue, in both the short and long term, predicates an urgent need to explore alternative approaches that base focussed intervention on exact-ingly defined molecular lesions. In this context proof-of -principle resides with the demonstration that Vitamin A can lead to clearing of acute progranulocytic leukaemia. Additional support comes from a small molecule designed to engage, and so disable, the abnormal tyrosine kinase receptor which characterises chronic granulocytic leukaemia. This oral tablet, STI 571, imatinib mesylate or Gleevec, is promising since it results in major cytogenetic responses but not without new challenges. One of the latter is drug resistance and this phenomenon illuminates the need for more research to better understand the emerging paradigm of target-specific cancer medicine.