Cell Cycle and Cancer Therapy

Cell Biology and Principles of Cancer Therapy

Treatment of cancers involving the breast and genital organs may involve surgery, chemotherapy,radiation therapy, or hormone therapy, used alone or in combination. The specific treatment plan depends on the type of cancer, the stage of the cancer, and the charac-teristics of the individual patient. Individualizing treatmentis an important aspect of cancer therapy.

CELL CYCLE AND CANCER THERAPY

Knowledge of the cell cycle is important in understand-ing cancer therapies. The ideal cancer treatment would be a drug that targets only cancer cells with no effect on healthy tissues.

In order to optimally target only cancerous tissue, it is imper-ative to understand not only how normal cells function, but also how cancer cells differ from normal cells.

Many treatments are based on the fact that cancer cells are constantly dividing, making them more vulnerable to agents that interfere with cell division.

The cell cycle consists of four phases (Fig. 40.1). Duringthe G₁ phase (postmitotic phase), RNA and protein syn-thesis, cell growth, and DNA repair take place. Once these processes are complete, the cell enters the S phase (syn-thesis phase), during which the DNA is completely repli-cated. The G₂ phase is a period of additional synthesis of RNA, protein, and specialized DNA. Cell division occurs during the M phase (mitosis). After mitosis, cells can again enter the G₁ phase, or can “drop out” of the cell cycle and enter a resting phase (G₀). Cells in G₀ do not engage in the synthetic activities characteristic of the cell cycle and are not vulnerable to therapies aimed at actively growing and dividing cells. The growth fraction is the proportion of cells in a tumor that are actively involved in cell division (i.e., not in the G₀ phase). The growth fraction of tumors decreases as they enlarge, because vascular supply and oxygen levels are decreased. Surgical removal of tumor tissue(cytoreductive debulking surgery) can result in G₀ cells reentering the cell cycle, thus making them more vulnerable to chemother-apy and radiation therapy.

The generation time is the length of the cell cycle, from one M phase to the next M phase. For a given cell type, the lengths of the S and M phases are relatively constant, whereas G₂ and especially G₁ vary. The variable length of G₁ can be explained by cells entering the resting phase (G₀) for a period and then reentering the cycle. The length of G₁ has a profound effect on the cell’s susceptibility to treatment.

Chemotherapeutic agents and radiation kill cancer cells by first-order kinetics. This means that each dose kills a con-stant fraction of tumor cells, instead of a constant number. The resulting clinical implication is that several intermittent doses are more likely to be curative than a single large dose.