Chemotherapy for
cancer is partly limited by the inability of drugs to act on poorly vascularized or avascularized areas of
tumors.
Tumor-targeting bacteria are capable of preferentially replicating in these poorly perfused regions. Some strains have been combined with chemotherapeutic agents and the results have been promising. However, no systematic work has been carried out to test the effect of bacteria on clinical modes of
chemotherapy, such as standard maximum tolerated dose (MTD) and novel low-dose metronomic (LDM)
chemotherapy. Here Salmonella typhimurium
VNP20009 was combined with
cyclophosphamide (CTX) at both MTD and LDM schedules in a murine
melanoma model. The results showed that
VNP20009 significantly improved the effects of all forms of CTX treatments. The combination of
VNP20009 and CTX led to a more significant decrease in
tumor microvessel density and serum
vascular endothelial growth factor (
VEGF) level, compared with either treatment alone. Furthermore, combination
therapy remarkably increased the number of bacteria within
tumors when compared with bacteria treatment alone. These findings suggest that
tumor-targeting bacteria, in conjunction with CTX at standard MTD and LDM regimens, might be of clinical value for the treatment of
melanoma.