Problems of Acquired Radioresistance of Cancer: Adaptation of Tumor Cells

Experience shows that malignant tumors of various microscopic structure which respond to initial irradiation may lose their radiosensitivity in part or whole during or after radiation therapy. Thus, they acquire various degrees of radioresistance, which, in the opinion of many observers, is one of the main causes of failure of radiation therapy. Little is known of the causes of this interesting and obviously important phenomenon. Ferroux, Regaud, and Samssanow (10), in experimental studies, found no demonstrable structural changes associated with decreased radiosensitivity of tumors. The various opinions in this field (2, 3, 13, 20, 21, 23) may be summarized as follows: 1. According to one theory, there is a certain selection of tumor cells present during the course of the first irradiation. The more sensitive cells become disintegrated and the more resistant ones retain their vitality. It has been assumed that each tumor consists of a conglomerate of resistant and sensitive cells which cannot be differentiated microscopically. The resistant cells are not destroyed in the course of irradiation and they are the seed for the growth of a new, more resistant cell strain (10, 23). 2. The hypothesis of induction, by irradiation, of a biological mutation of the cancer cells, i.e., a change in their “character,” was advanced as early as 1905 (24). It has been stated, for instance, that an alveolar cancer of the breast became scirrhous after roentgen irradiation. This theory has had many followers, and the belief. has been repeatedly expressed that after irradiation a new type of radioresistant cell may develop (20). 3. According to still another view, a functional change affects the connective tissue in which the neoplastic cells are embedded. Injured by irradiation, this no longer reacts to the presence of the tumor and no longer hinders the relentless growth of tumor cells (13). A number of investigators (16, 17, 18) believe that connective-tissue damage by irradiation may be present even though no microscopic signs of retrogressive changes are observed. The phenomenon of radiologic induction of biological mutations has been attributed by early French authors to a common property of the radiant energy, namely, that of producing more highly differentiated structures from anaplastic and less highly differentiated tissues (maturation évolutive). Increased cornification of the epithelium of the skin and transformation of squamous epithelium of mucous membranes into excessively cornified epithelium after irradiation are well known. The microscopic demonstration of the development of cornified structures, following irradiation, in basal-cell cancers (23), which as a rule do not cornify, substantiates this theory to a certain extent. I have had frequent opportunities to corroborate these observations.