Somatic evolution in cancer

Somatic evolution is the accumulation of mutations and epimutations in somatic cells (the cells of a body, as opposed to germplasm and stem cells) during a lifetime, and the effects of those mutations and epimutations on the fitness of those cells. This evolutionary process has first been shown by the studies of Bert Vogelstein in colon cancer. Somatic evolution is important in the process of aging as well as the development of some diseases, including cancer. Somatic evolution is the accumulation of mutations and epimutations in somatic cells (the cells of a body, as opposed to germplasm and stem cells) during a lifetime, and the effects of those mutations and epimutations on the fitness of those cells. This evolutionary process has first been shown by the studies of Bert Vogelstein in colon cancer. Somatic evolution is important in the process of aging as well as the development of some diseases, including cancer. Cells in pre-malignant and malignant neoplasms (tumors) evolve by natural selection. This accounts for how cancer develops from normal tissue and why it has been difficult to cure. There are three necessary and sufficient conditions for natural selection, all of which are met in a neoplasm: Cells in neoplasms compete for resources, such as oxygen and glucose, as well as space. Thus, a cell that acquires a mutation that increases its fitness will generate more daughter cells than competitor cells that lack that mutation. In this way, a population of mutant cells, called a clone, can expand in the neoplasm. Clonal expansion is the signature of natural selection in cancer. Cancer therapies act as a form of artificial selection, killing sensitive cancer cells, but leaving behind resistant cells. Often the tumor will regrow from those resistant cells, the patient will relapse, and the therapy that had been previously used will no longer kill the cancer cells. This selection for resistance is similar to the repeatedly spraying crops with a pesticide and selecting for resistant pests until the pesticide is no longer effective. Modern descriptions of biological evolution will typically elaborate on major contributing factors to evolution such as the formation of local micro-environments, mutational robustness, molecular degeneracy, and cryptic genetic variation. Many of these contributing factors in evolution have been isolated and described for cancer. Cancer is a classic example of what evolutionary biologists call multilevel selection: at the level of the organism, cancer is usually fatal so there is selection for genes and the organization of tissues that suppress cancer. At the level of the cell, there is selection for increased cell proliferation and survival, such that a mutant cell that acquires one of the hallmarks of cancer (see below), will have a competitive advantage over cells that have not acquired the hallmark. Thus, at the level of the cell there is selection for cancer. The earliest ideas about neoplastic evolution come from Boveri who proposed that tumors originated in chromosomal abnormalities passed on to daughter cells. In the decades that followed, cancer was recognized as having a clonal origin associated with chromosomal aberrations. Early mathematical modeling of cancer, by Armitage and Doll, set the stage for the future development of the somatic evolutionary theory of cancer. Armitage and Doll explained the cancer incidence data, as a function of age, as a process of the sequential accumulation of somatic mutations (or other rate limiting steps). Advances in cytogenetics facilitated discovery of chromosome abnormalities in neoplasms, including the Philadelphia chromosome in chronic myelogenous leukemia and translocations in acute myeloblastic leukemia. Sequences of karyotypes replacing one another in a tumor were observed as it progressed. Researchers hypothesized that cancer evolves in a sequence of chromosomal mutations and selection and that therapy may further select clones.