On the biological significance of tumor growth (chapter 3)

RUGGIERO, RAÚL A.; BUSTUOABAD, OSCAR D.; CHIARELLA, PAULA; BRUZZO, JUAN; MEISS, ROBERTO P.

Cell Growth Processes: New Research

Nova Science Publishers

Lugar: Nueva York; Año: 2008; p. 89 - 121

Despite their wide differences, most theories about cancer proposed during the past century agree that cancer is a biological nonsense for the organism in which it originates since cancer cells are believed to be autonomous (or relatively autonomous), meaning that they are not subject to the rules and regulations that control normal cell proliferation and differentiation in the organism. In this chapter we have challenged this interpretation on the basis that, throughout the animal kingdom, cancer seems to arise only in organs and tissues that display lost or diminished regenerative ability. In these organs, any injury causing loss of cells or cellular function cannot be compensated by cellular division and in consequence, the original size and function cannot be restored. We suggest that this situation induces a crisis, which, through putative danger signals resulting from retardation of tissue repair, acceleration of cell loss and functional compromise, might promote some degree of variability in the remaining live but arrested cells of the injured organ. The outcome of this situation would be the emergence, by chance, of a genetically or epigenetically modified cell variant bearing mitotic ability to respond to the reparative signal. This new variant would begin to divide and if it were poorly functional or non-functional, the organ would be numerically but not functionally restored. In consequence, it would not score the regeneration as effective and it would continue to send mitotic signals to restore the lost or diminished organ function. As a result, the new variant would grow over and over and the outcome would be a tumor.  According to this hypothesis, cancer would not be an autonomous entity disobeying the mechanisms controlling cell proliferation; in fact, in the injured organ which has its regenerative ability lost or diminished, a tumor cell would be the only one able to respond to the demand to proliferate surrounded by “normal” but arrested cells that cannot respond to that signal. According to this interpretation, cancer would have a profound biological sense: it would be the ultimate attempt to restore organ functions and structures that have been lost or altered by aging and noxious environmental agents. However, unlike normal structures, cancer would have no physiological value, because the usually poor or non-functional nature of its cells would make their reparative task unattainable. The hypothesis advanced in this chapter might have significant practical implications. All conventional therapies against cancer attempt to kill all tumor cells. However, according to our hypothesis, the problem might not be solved even if all the tumor cells were eradicated. In effect, if the organ failure remained, new tumor cells would emerge and the tumor would reinitiate its progressive growth in response to the permanent regenerative signal of the non-restored organ. Therefore, efficient anti-cancer therapy should combine an attack against the tumor cells themselves with the correction of the organ failure, which, according to this hypothesis, would be in the core of the cancer problem.