The programmed death of a cell is called apoptosis, an event usually caused by internal damage or by signals from surrounding tissues. Apoptosis and cancer are connected in two important ways. First, tumors cannot grow if the normal safety system within the body detects them and triggers their self-destruction, so cancers often block the mechanisms by which the body marks uncontrolled tissue growth for apoptosis. Secondly, cancer cells inactivate the genes that encode the necessary proteins to destroy malignant cells. Chemotherapies take advantage of the relationship between apoptosis and cancer by damaging tumors and marking them for death.
Apoptosis occurs when chemical signals initiate a process of self-destruction within a cell, through changes in the membrane, degradation of the DNA in the nucleus, and the digestion of cellular proteins by specialized enzymes. There are two types of pathways that will make a cell undergo apoptosis: the intrinsic, which is initiated by DNA mutations, and the extrinsic, which takes its cues from outside of the cell. The extrinsic pathway can be triggered by hormones, toxins, and other molecules capable of activating special locations on the cell known as death receptors.
During the early stages of tumor formation, mutations within the DNA occur that alter the relationship between apoptosis and cancer that permit uncontrolled cell growth. Cancer involves pathological changes to the cycle by which cells reproduce and proliferate, events that normally trigger apoptosis when they are detected within healthy cells. This is sometimes done by suppressing the genes' coding for important proteins that the body uses to signal cancerous tissues for elimination by apoptosis. Tumors may also secrete chemical messengers that confuse or block the process that would ordinarily order cancer cells to undergo self-destruction.
An important gene, p53, encodes for messenger proteins that cause apoptosis. Some cancers caused by viruses suppress the activation of this gene and make tumor cells less responsive to activation of the death receptors. Whether caused by viruses or not, cellular production of growth-enhancing substances is increased in tumors. Normally, the body responds to uncontrolled proliferation of a particular cell type by causing mass apoptosis, but during oncogenesis — the formation of cancer — the balance between apoptosis and cancer skews toward cell growth, not death.
Chemotherapeutic treatments often depend on the relationship between apoptosis and cancer. Most of these drugs also interfere with DNA synthesis and cellular division or growth, but these mechanisms ultimately work to destroy the tumorous cells before they divide and make more copies of themselves. Various drugs activate different points along the pathway that leads to programmed cell death as well, sometimes by increasing the sensitivity of the death receptors on the tumor cells. Since some malignancies no longer respond to self-destruct signals, scientists are interested in developing chemotherapies that can induce the natural apoptosis events directly.