Clues to the Etiology, Pathology, and Therapy of Cancer Provided by Analogies With Transplantation Disease23

Abstract

The hypothesis is developed that a malignant tumor arises from a single cell that has suffered loss or inactivation of a single gene, if in heterozygous condition, or of both alleles if homozygous. The relevant genes are considered to be those determining the formation of histocompatibility antigens. The precancer cell lacking one (or more in case of multiple gene loss) of these antigens responds to the proliferative stimulus continuously provided by the, now foreign, “host” antigen, in the same manner as do ordinary antibody-forming cells to the administration of a foreign antigen. Production of cell-fixed and, to some extent, of circulating antibodies by the tumor cells is assumed to be primarily responsible for the cancer syndrome, an experimental counterpart of which is represented by the transplantation diseases such as “runt disease.” Directions of exploration of therapeutic measures are indicated primarily on the basis of utilization of the principle of allergic damage to cells, and, as more remote prospects, by supplying missing deoxyribonucleic acid (DNA) or ribonucleic acid (RNA), and by autoimmunization procedures.