Neoplastic growth: the consequence of evolutionary malignant resistance to chronic damage for survival of cells (review of a new theory of the origin of cancer).

In the present review, a new theory that the mechanisms of general evolutionary persistent resistance to damaging factors are closely related to the development of tumour cells is introduced. Evolutionary resistance and its variability have an immense power to drive and control the process of carcinogenesis and the success of microbial and antitumour chemotherapy. First, this phenomenon of adaptation is characteristic of microbial cells whose resistance to antibiotics and other chemotherapeutic drugs is manifested through ATP-dependent transmembrane transporters. The structure and function of some multidrug transporters of resistance are conserved from microorganisms to mammals. When somatic cells are exposed to carcinogens and develop into tumour cells, they also acquire resistance to the toxic effects of carcinogens through these same transmembrane transporters (P-glycoprotein, glutathione S-transferases and other products of evolutionary resistance-related genes arisen for detoxification and exportation of cytotoxic xenobiotics and drugs). Cancerous cells acquire a persistent evolutionary resistance to chemotherapy drugs or irradiation through the same ATP-dependent transporters encountered in prokaryotic and eukaryotic cells. The mechanism of acquired resistance of cells to damaging factors, which becomes manifested during tumorigenic process formation, is a general biological law of primary significance in carcinogenesis. This resistance can be called malignant as, once formed, it does not disappear, as does also a clone of malignant cells. In tumorous cells, the mutagenic processes, morphological and functional modifications are a mechanism of secondary significance in carcinogenesis, contributing to formation of damage-resistant cells. This mechanism characterizes the processes of simplification arising in damage-resistant cells. Such cells acquire parasitic features. To survive under unfavourable conditions, they get adapted as if returning down the evolutionary stairs back to a more primitive stage of atavistic regression, which is characteristic of primitive forms of existence. Therefore they cease obeying the growth-regulating mechanisms in the organism and acquire the potential of unlimited division and accelerated growth (metastases) as do unicellular organisms or their forms resistant to damaging factors in the environment and in the host organism. Thus, cancer is a natural self-protective response of the damaged cells to the biological, physical and chemical damage and oxidative stress. This response has been developed in the process of evolution under the impact of the general biological Darwinian law of nature--to survive through variability and adaptation to the changed environmental conditions. Thus, malignization is the consequence of an evolutionary variety of the general biological resistance of cells to damage and stress in order to survive.