Cidofovir treatment improves the pathology caused by the growth of human papillomavirus-positive cervical carcinoma xenografts in athymic nude mice

Reduced tumorigenicity and pathogenicity of cervical carcinoma SiHa cells selected for resistance to cidofovir

“…Four weeks intratumoral treatment with CDV of athymic nude mice bearing the SiHa CDV xenografts resulted in a moderate but not significant effect on tumor growth (Additional file 5). In contrast, the same treatment given to mice harboring the SiHa parental xenograft caused a remarkable and significant suppression of tumor growth, in agreement with our previous report [24]. Interestingly, tumor size was significantly lower in the SiHa CDV cohort than in the SiHa parental group.…”

“…Cidofovir antitumor properties were also demonstrated in different animal models of tumors related to transforming viruses, including Epstein-Barr virus-associated nasopharyngeal carcinoma [21] and HPV-induced cervical carcinoma [22-24] xenografts in athymic-nude mice, polyomavirus-induced hemangiomas in rats [25] and hemangiosarcoma development in mice [26]. Also, CDV proved effective against cottontail rabbit papillomavirus in the domestic rabbit model [27].…”

“…We have recently shown that besides inhibition of tumor growth, intratumoral CDV administration had a beneficial effect on the pathology associated with the growth of cervical carcinoma cells in athymic nude mice as demonstrated by a favorable effect on body weight gain, reduced splenomegaly and lower inflammatory state in animals that received the compound versus the placebo-treated group [24]. Furthermore, a whole genome gene expression profiling performed on CDV-treated malignant cells and normal keratinocytes allowed us to identify unique signatures in tumor cells compared to normal keratinocytes pointing to a selective drug effect [28].…”

Insights into the mechanism of action of cidofovir and other acyclic nucleoside phosphonates against polyoma- and papillomaviruses and non-viral induced neoplasia

“…CDV was shown not only to inhibit the growth of cervical carcinoma xenografts in athymic nude mice (Andrei et al, 1998b;Yang et al, 2010), but also to improve the pathology associated with tumor growth (De Schutter et al, 2013a). Intratumoral administration of CDV resulted in a beneficial effect on body weight gain, a reduction in splenomegaly, a partial restoration of tryptophan catabolism, and diminished the inflammatory state induced by the xenografts.…”

“…Also, a decrease in tumor (human)-derived cytokines was measured following CDV administration. Furthermore, the positive effects of intratumoral CDV (including increased body weight gain and decreased inflammatory response) correlated with a reduction in tumor size (De Schutter et al, 2013a).…”