Evolving models of tumor origin and progression

History of cancer disease models clearly illustrates the evolving nature of these concepts. Since such models undergo continual revisions and additions as a result of underlying medical research, they also tend to reorganize knowledge and allow perceiving previously unseen relationships. Growth of medical thought has been influenced for many centuries by an ancient Hippocratic concept of disease seen as a disturbance in bodily "humors." True mechanisms of cell and tissue injury started to be elucidated only with the advent of postmortem pathological findings. Concerning cancer, when first disease-producing bacteria were identified in the nineteenth century, also neoplasms were treated as infectious diseases. Foreign organisms were thought to be present inside tumors. However, this hypothesis could not be confirmed by microscopic or histochemical studies. The latter suggested, instead, that tumors were rather formed by abnormal cells. Cancer was then started to be regarded as a disease of cells. This interpretation was radically altered by later developments in genetics which suggested that neoplasms can be treated as genetic diseases as pathologic cellular lesions are caused by mutations in specific genes. More recent models have compared carcinogenesis to evolutionary processes. Due to genetic instability, successive mutations, appearing in cells, lead to selection of cancer cells which feature specific phenotypic traits. The newest data indicate that there may be also a link between cancer and mutated stem cells. The review discusses main concepts of tumor origin forwarded since the beginnings of the nineteenth century.