TY - CHAP M1 - Book, Section TI - Discovery and Evaluation of Anticancer Drugs A1 - Schimmer, Aaron D. A1 - Tannock, Ian F. A2 - Tannock, Ian F. A2 - Hill, Richard P. A2 - Bristow, Robert G. A2 - Harrington, Lea Y1 - 2016 N1 - T2 - The Basic Science of Oncology, 5e AB - Chemotherapy is used primarily as (a) the major treatment modality for a few types of malignancies, such as Hodgkin disease and other hematopoietic cancers, acute leukemia in children, and testicular cancer in men; (b) palliative treatment for many types of advanced cancers; and (c) adjuvant treatment before, during, or after local treatment (surgery and/or radiotherapy) with the aim of both eradicating occult micrometastases and of improving local control of the primary tumor. Such treatments usually involve a combination of drugs. The most important factors underlying the successful use of drugs in combination are (a) the ability to combine drugs at close to full tolerated doses with additive effects against tumors and less-than-additive toxicities to normal tissues, and (b) the expectation that drug combinations will include at least 1 drug to which the tumor is sensitive. Since the first documented clinical use of chemotherapy in 1942, when the alkylating agent nitrogen mustard was used to obtain a brief clinical remission in a patient with lymphoma, about 45 cytotoxic drugs or biological agents (excluding hormonal agents) have been licensed for use in North America, and several more are undergoing clinical trials. The pharmacology of many of these agents is described in Chapter 18. In recent years, new types of anticancer agents have been developed, including monoclonal antibodies (eg, rituximab, trastuzumab, and bevacizumab) that target cell-surface receptors, and small molecules that interact with various cell signaling pathways (eg, imatinib). These newer agents represent a substantial shift in emphasis in anticancer drug therapy. In contrast to conventional cytotoxic agents, which usually target proliferating cells and interact with DNA, the newer agents target specific metabolic pathways that interfere with various functions of the cell, including those that promote cell division (trastuzumab, imatinib) or contribute to immune-mediated cellular damage (rituximab). Other agents, such as those that inhibit angiogenesis (eg, bevacizumab; see Chap. 11, Sec. 11.7.1) act indirectly to inhibit tumor growth. SN - PB - McGraw-Hill Education Medical CY - New York, NY Y2 - 2024/03/28 UR - hemonc.mhmedical.com/content.aspx?aid=1127473183 ER -