CCNS drug

Information on cell and population kinetics of cancer cells explains, in part, the limited effectiveness of most available anticancer drugs. A schematic summary of cell cycle kinetics is presented in Figure 54-2. This information is relevant to the mode of action, indications, and scheduling of cell cycle-specific (CCS) and cell cycle-nonspecific (CCNS) drugs. Agents falling into these two major classes are summarized in Table 54-1. 

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... 

Mechanisms These anthracyclines can intercalate between base pairs, inhibit topoisomerase II, and generate free radicals. They block the synthesis of RNA and DNA and cause DNA strand scission. Membrane disruption also occurs. Anthracyclines are CCNS drugs. 

Mechanisms and pharmacokinetics Dactinomycin is a CCNS drug that binds to double-stranded DNA and inhibits DNA-dependent RNA synthesis. Dactinomycin must be given parenterally, and both intact drug and metabolites are excreted in the bile. 

Mechanisms and pharmacokinetics Mitomycin is a CCNS drug that is metabolized by liver enzymes to form an alkylating agent which cross-links DNA. Mitomycin is given intravenously and is rapidly cleared via hepatic metabolism. 

Recruitment strategy in cancer chemotherapy involves the initial use of a CCNS drug (eg, doxorubicin) to achieve a significant log kill. This results in the recruitment into cell division of resting... 

Drugs acting on nonproliferating cells are cell-cycle nonspecific (CCNS)—dose-dependent. 

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