hematology and oncology
Cellular and Molecular Basis of Cancer
Cellular Kinetics
Generation time is the time required for a cell to complete a cycle in cell division (see figure The cell cycle ) and give rise to 2 daughter cells. Cancer cells, particularly those arising from the bone marrow or lymphatic system, may have a short generation time, and there usually are a smaller percentage of cells in G0 (resting phase). Initial exponential tumor growth is followed by a plateau phase when cell death nearly equals the rate of formation of daughter cells. The slowing in growth rate may be related to exhaustion of the supply of nutrients and oxygen for the rapidly expanding tumor. Small tumors have a greater percentage of actively dividing cells than do large tumors. A subpopulation of cells within a cancer has the properties of stem cells. Thus, these cells are capable of entering a proliferative state. They are also less susceptible to injury by drugs or irradiation. They are believed to repopulate cancers after chemotherapy and/or radiation treatment. The cellular kinetics of particular cancers is an important consideration in the design of antineoplastic drug regimens and may influence the dosing schedules and timing intervals of treatment. Many antineoplastic drugs, such as antimetabolites, are most effective when cells are actively dividing. Some drugs work only during a specific phase of the cell cycle, requiring prolonged administration to catch dividing cells during the phase of maximal sensitivity. G0=resting phase (nonproliferation of cells); G1=variable pre-DNA synthetic phase (12 h to a few days); S=DNA synthesis (usually 2 to 4 h); G2=post-DNA synthesis (2 to 4 h)—a tetraploid quantity of DNA is found within cells; M1=mitosis (1 to 2 h). 