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20.1
Cancer can result from the abnormal proliferation of any type of cell. The most important distinction is between benign tumors, which remain confined to their site of origin, and malignant tumors, which can invade normal tissues and spread throughout the body. Tumors develop from single cells that begin to proliferate abnormally. Additional mutations lead to the selection of cells with progressively increasing capacities for proliferation and metastasis. The uncontrolled proliferation of cancer cells is reflected in reduced requirements for growth factors and lack of inhibition by cell-cell contact. The characteristic failure of cancer cells to undergo apoptosis also contributes substantially to tumor development. Radiation and most chemical carcinogens act by damaging DNA and inducing mutations. Viruses also cause cancer in both humans and other species.
20.2
The first oncogene to be identified was the src gene of RSV. Subsequent studies have identified more than two dozen distinct oncogenes in different retroviruses. Retroviral oncogenes are abnormally expressed and mutated forms of normal cell genes, called proto-oncogenes. Cellular oncogenes are activated by point mutations, DNA rearrangements, and gene amplification in human cancers. Some of these human tumor oncogenes, such as the ras genes, are cellular homologs of oncogenes that were first described in retroviruses. Many oncogene proteins function as elements of signaling pathways that stimulate cell proliferation. The genes that encode cyclin D1, Cdk4, and Cdk6 can also act as oncogenes by stimulating cell cycle progression. Other oncogene proteins interfere with cell differentiation, and oncogenes encoding PI 3-kinase, Akt, and Bcl-2 inhibit apoptosis.
20.3
In contrast with oncogenes, tumor suppressor genes inhibit tumor development. Loss or mutational inactivation of tumor suppressor genes, including Rb and p53, contributes to the development of a wide variety of human cancers. The proteins encoded by most tumor suppressor genes act as inhibitors of cell proliferation or survival. Mutations in both oncogenes and tumor suppressor genes contribute to the progressive development of human cancers. The many different genes that can contribute to tumor development affect the activities of a relatively small number of cell regulatory pathways.
20.4
Genetic testing to identify individuals with inherited mutations in oncogenes or tumor suppressor genes may allow early detection and more effective treatment of high-risk patients. The development of drugs targeted against specific oncogenes has led to the discovery of new therapeutic agents that act selectively against cancer cells. Advances in immunotherapy have led to effective cancer treatments by strengthening the immune response against cancer cells.