Preclinical activity of metronomic regimens with alkylating agents and antimetabolites

Abstract

We know that the same drug, when administered at different doses, schedules, and moments, can produce completely different effects on tumor progression. For the last 10 years, research has been trying to unravel how metronomic chemotherapy antitumor effects arise. Numerous in vitro and in vivo studies have provided evidence that the main effects of metronomic chemotherapy are related not only to tumor angiogenesis but also to the cancer cells, tumor environment, and stromal component. Nevertheless, there remain large gaps in our knowledge of the molecular mechanisms by which these effects arise. This review summarizes part of the preclinical research, performed with those alkylating agents and antimetabolites most commonly used in the metronomic chemotherapy approach. Much of this report concerns cyclophosphamide, since, in this context, it is the most widely explored drug so far. The report also draws attention to the numerous cancer cell lines and the main murine models used.