Cancers are characterized by unregulated cell division, avoidance of cell death, tissue invasion, and the ability to metastasize. A neoplasm is benign when it grows in an unregulated fashion without tissue invasion. The presence of unregulated growth and tissue invasion is characteristic of malignant neoplasms. Cancers are named based on their origin: those derived from epithelial tissue are called carcinomas, those derived from mesenchymal tissues are sarcomas, and those derived from hematopoietic tissue are leukemias, lymphomas, and plasma cell dyscrasias (including multiple myeloma).
Cancers nearly always arise as a consequence of genetic alterations, the vast majority of which begin in a single cell and therefore are monoclonal in origin. However, because a wide variety of genetic and epigenetic changes can occur in different cells within malignant tumors over time, most cancers are characterized by marked heterogeneity in the populations of cells. This heterogeneity significantly complicates the treatment of most cancers because it is likely that there are subsets of cells that will be resistant to therapy and will therefore survive and proliferate even if the majority of cells are killed.
A few cancers appear to, at least initially, be primarily driven by an alteration in a dominant gene that produces uncontrolled cell proliferation. Examples include chronic myeloid leukemia (abl), about half of melanomas (braf), Burkitt’s lymphoma (c-myc), and subsets of lung adenocarcinomas (egfr, alk, ros1, and ret). The genes that can promote cell growth when altered are often called oncogenes. They were first identified as critical elements of viruses that cause animal tumors; it was subsequently found that the viral genes had normal counterparts with important functions in the cell and had been captured and mutated by viruses as they passed from host to host.
However, the vast majority of human cancers are characterized by a multiple-step process involving many genetic abnormalities, each of which contributes to the loss of control of cell proliferation and differentiation and the acquisition of capabilities, such as tissue invasion, the ability to metastasize, and angiogenesis. These properties are not found in the normal adult cell from which the tumor is derived. Indeed, normal cells have a large number of safeguards against uncontrolled proliferation and invasion. Many cancers go through recognizable steps of progressively more abnormal phenotypes: hyperplasia, to adenoma, to dysplasia, to carcinoma in situ, to invasive cancer with the ability to metastasize (Table 26-1). For most cancers, these changes occur over a prolonged period of time, usually many years.
TABLE 26-1Phenotypic Characteristics of Malignant Cells |Favorite Table|Download (.pdf) TABLE 26-1 Phenotypic Characteristics of Malignant Cells
Deregulated cell proliferation: Loss of function of negative growth regulators (tumor-suppressor genes, i.e., Rb, p53), and increased action of positive growth regulators (oncogenes, i.e., Ras, Myc). Leads to ...