Chemotherapy and novel systemic therapies

The emergence of chemotherapy in the 1950s has led to the availability of systemic therapies for patients with hematologic malignancies and advanced solid tumors. These advances proved the concept of using chemotherapy to indeed cure cancer, in case of hematologic malignancies, and provided the rationale for integrating chemotherapy into combined modality approaches for solid tumors. Skipper et al. (1) has defined the invariable inverse relation between cell number and curability in a leukemia model. Therefore, when treatment failed in sensitive cell lines, it was thought to be attributed to the initial high tumor burden, which was too high for even potentially curative doses of chemotherapy to eradicate cancer cells. This relationship could be applied to other hematologic malignancies and solid tumors. However, recent advances in our understanding of the molecular pathways by which chemotherapy exerts its cytotoxic activity, and by which genetic change can result in resistance to drug therapy, has provided a basis for our understanding of chemoresistance and the development of innovative therapeutic strategies.