Use of Xanthinol Nicotinate as a co-treatment for radio- and chemo-therapy in experimental tumors.

The tumor micro-environment plays a key role in the tumor resistance to cytotoxic treatments. It has been demonstrated that it is possible to modulate the tumor microenvironment to potentiate anti-cancer therapy. Here, we made the hypothesis that the vasoactive agent xanthinol nicotinate (XN) could be an important modulator of the tumor perfusion and oxygenation. Using functional non invasive techniques (in vivo EPR oximetry and dynamic contrast enhanced MRI), we were able to define a time window in which tumor oxygenation, flow and permeability were significantly increased in the TLT tumor model implanted in muscles of mice. As a consequence of the alleviation of tumor hypoxia, we found out that XN was able to radiosensitize the tumors when applying 10 Gy of X-Rays during the reoxygenation of the tumors (enhancement in radiation response of 1.4). Moreover, the administration of cyclosphosphamide (50 mg/kg) used as a chemotherapeutic agent was more efficient when applying the treatment after XN administration (enhancement in response to chemotherapy of 2.7). These results show the importance of the dynamic evolution of the tumor microenvironment on the response to treatments, and that XN is an efficient modulator of the tumor hemodynamics that may potentiate cytotoxic treatments.