Revisiting the phenomenon of concomitant tumor resistance and its impact on established metastases of murine and human origin

Abstract

Concomitant tumor resistance (CR) is a phenomenon in which a tumor-bearing host inhibits the growthofsecondary tumor implants. The relevance of CR to mechanisms of metastases control has been highlightedby numerous observations showing that the removal of human and murine tumors may be followed by anabrupt increase in metastatic growth. This body of evidence suggests that, upon certain circumstances, aprimary tumor would exert a controlling action on its metastases that can be considered as naturalsecondary tumor implants spontaneously developed during the primary tumor growth.In this article werevised both former and recent evidence accounting for this fact in both experimental and clinical settingsand discussed the situations in which tumor removal would be or would not be recommended. In addition,we analyzed the different mechanisms historically proposed to explain CR especially focusing on the lastinvestigations of our laboratory concerning the importance of tyrosine isomers as mediators of thephenomenon of CR and on their capacity to inhibit established metastases of both murine and human origin.Our investigations aimed to elucidate the molecular basis of the phenomenon of CR might stimulatethedesign of new strategies aimed to limit the development of metastases,an issue of critical importance forpatients afflicted by malignant diseases.