Cancer chemotherapy remains an intriguing area of pharmacology. On the one hand, use of anticancer drugs produces high rates of cure of diseases, which, without chemotherapy, result in extremely high mortality rates (eg, acute lymphocytic leukemia in children, testicular cancer, and Hodgkin's lymphoma). On the other hand, some types of cancer are barely affected by currently available drugs. Furthermore, as a group, the anticancer drugs are more toxic than any other pharmaceutic agents, and thus their benefit must be carefully weighed against their risks. Many of the available drugs are cytotoxic agents that act on all dividing cells, cancerous or normal. The ultimate goal in cancer chemotherapy is to use advances in cell biology to develop drugs that selectively target specific cancer cells. A few such agents are in clinical use, and many more are in development.
|Cell cycle-nonspecific (CCNS) drug||An anticancer agent that acts on tumor stem cells when they are traversing the cell cycle and when they are in the resting phase|
|Cell cycle-specific (CCS) drug||An anticancer agent that acts selectively on tumor stem cells when they are traversing the cell cycle and not when they are in the G0 phase|
|Growth fraction||The proportion of cells in a tumor population that are actively dividing|
|Myelosuppressant||A drug that suppresses the formation of mature blood cells such as erythrocytes, leukocytes, and platelets. This effect is also known as "bone marrow suppression"|
|Oncogene||A mutant form of a normal gene that is found in naturally occurring tumors and which, when expressed in noncancerous cells, causes them to behave like cancer cells|
Cancer cell population kinetics and the cancer cell cycle are important determinants of the actions and clinical uses of anticancer drugs. Some anticancer drugs exert their actions on cells undergoing cycling (cell cycle-specific [CCS] drugs), and others (cell cycle-nonspecific [CCNS] drugs) kill tumor cells in both cycling and resting phases of the cell cycle (although cycling cell are more sensitive). CCS drugs are usually most effective when cells are in a specific phase of the cell cycle (Figure 54–1). Both types of drugs are particularly effective when a large proportion of the tumor cells are proliferating (ie, when the growth fraction is high).
Phases of the cell cycle that are susceptible to the actions of cell cycle-specific (CCS) drugs. All dividing cells—normal and neoplastic—must traverse these cell cycle phases before and during cell division. Tumor cells are usually most responsive to specific drugs (or drug groups) in the phases indicated. Cell cycle-nonspecific (CCNS) drugs act on tumor cells while they are actively cycling and while they are in the resting phase (G0). (Reproduced and modified, with permission, from Katzung BG, editor: Basic & Clinical Pharmacology,...