title: Resistance to cancer chemotherapy.
abstract: Human cancers are either refractory to chemotherapy, or acquire resistance to it. Although acquired resistance to chemotherapy is generally ascribed to the drug itself, it may be linked with the nature of neoplasia, since normal tissues e.g. gastrointestinal mucosa or bone marrow, do not seem to acquire resistance and their perpetuating sensitivity even undermines effective treatment. According to the theory presented herewith, chemotherapy ultimately fails since it is based on wrong premises. Cancer is regarded here as a metabolic deficiency, originating in stem cell destruction. Besides serving as tissue progenitors, stem cells are postulated to secrete a vital substance 'A' necessary for proper tissue function. Carcinogens interfere with 'A' production mainly by destroying stem cells, which the organism is incapable of fully replenishing, so that less 'A' is produced. This irreversible 'A' deficiency may be replenished solely by a substitute, or substance 'B', produced by a specialized organ, the neoplasm. Since carcinogens continue depleting additional stem cells, the deficiency worsens. In order to keep up with increasing demand the neoplasm has to proliferate more and more until it reaches a stage of decompensation when the harm inflicted by it outweighs its benefit. Stem cell depletion is regarded here as the common final pathway of carcinogens. The theory predicts that following a supply of 'A' producing stem cells or inactivated 'B' producing neoplastic stem cells, the tumor will regress. Tumor regression is achievable also by diminishing the demand for the missing metabolites, which may be accomplished by chemotherapy. 'A' and 'B' are consumed mainly by transitional cells. Upon their elimination the demand for 'A' declines and the tumor may wane. This is regarded here as the main role of chemotherapy in cancer, while its tumoricidal potency is indicated solely for repairing tumor induced function loss. It is proposed here that the good response to chemotherapy by Hodgkin's disease and seminoma is linked with their being partially infective. Both start as genuine smouldering infections turning later into neoplasms. While chemotherapy is adequate only during the infective phase, it is met with mounting resistance when applied during the neoplastic phase.
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002100:Cachexia; D002273:Carcinogens / Q000494:pharmacology; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D004351:Drug Resistance; D006689:Hodgkin Disease / Q000188:drug therapy; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008941:Spindle Apparatus / Q000187:drug effects; D013234:Stem Cells / Q000473:pathology / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D002273:Carcinogens; D004247:DNA