Tumors as caricatures of the process of tissue renewal: prospects for therapy by directing differentiation.

A concept of neoplasms, based upon developmental and oncological principles, states that carcinomas are caricatures of tissue renewal, in that they are composed of a mixture of malignant stem cells, which have a marked capacity for proliferation and a limited capacity for differentiation under normal homeostatic conditions, and of the differentiated, possibly benign, progeny of these malignant cells. The concept brings order to the facts about carcinoma, has predictive value for embryogenesis, and indicates possibilities for differentiation therapy. One such possibility assumes on the basis of experimentation in vitro that malignant stem cells can be induced to differentiate into postmitotic cells by application of chemicals. Another suggests study of naturally occurring substances which regulate cell proliferation and differentiation in adult tissues. The other possibility, based upon experiments in vivo and in vitro, indicates that embryonic fields are capable of converting their closely corresponding malignant lineages into apparently normal lineages responsive to homeostatic control. Induced differentiation of embryonal carcinoma has been achieved in vivo with improvement in longevity of the host and in some cases with apparent cure. However, ultimate success of treatment based upon turning malignant cells into benign cells will depend upon the nature of the benign cells. Will they remain benign?