Low dose angiostatic treatment counteracts radiotherapy-induced tumor perfusion and enhances the anti-tumor effect

摘要: The extent of tumor oxygenation is an important factor contributing to the efficacy radiation therapy (RTx). Interestingly, several preclinical studies have shown benefit combining RTx with drugs that inhibit blood vessel growth, i.e. angiostatic therapy. Recent findings show proper scheduling both treatment modalities allows dose reduction without affecting therapeutic efficacy. We found whilst low sunitinib (20 mg/kg/day) did not affect growth xenograft HT29 colon carcinoma tumors in nude mice, combination either single (1x 5Gy) or fractionated (5x 2Gy/week, up 3 weeks) substantially hampered compared alone. To better understand interaction between and therapy, we explored effects on angiogenesis tissue perfusion. DCE-MRI analyses revealed resulted enhanced perfusion after two weeks treatment. This mainly occurred center was accompanied by increased viability decreased hypoxia. These were expression pro-angiogenic factors VEGF PlGF. contrast ultrasonography showed increase counteracted low-dose sunitinib. Overall, these data give insight dynamics during conventional 2 Gy provide a rationale combine palliative as well curative setting.