Optimization of tumor radiotherapy with modulators of cell metabolism: towards clinical applications

Danhier, Pierre [UCL] De Saedeleer, Christophe [UCL] Karroum, Oussama [UCL] De Preter, Géraldine [UCL] Porporato, Paolo [UCL] Jordan, Bénédicte [UCL] Gallez, Bernard [UCL] Sonveaux, Pierre [UCL]

Most solid tumors are characterized by oxygen instabilities creating regions of hypoxia that are detrimental to radiotherapy. Because after surgery radiotherapy alone or in combination with other interventions is a first-line treatment for many malignancies, strategies aimed at increasing the tumor pO2 homogeneously in tumors have been the focus of intense research over the last decades. Among other approaches having proved preclinical and/or clinical utility, those targeting tumor metabolism in order redirect oxygen from a metabolic fate to the stabilization of radiation-induced DNA damage are highly relevant. They include heat therapy (hyperthermia and hypothermia), drugs targeting glucose and lactate metabolism, nitric oxide donors and inducers, anti-inflammatory drugs, and mitogen-activated protein kinase (MAPK) pathway inhibitors. While many of these drugs and interventions are in clinical use often for other pathologies than cancer, their utility as adjuvant treatments with radiotherapy has been proven preclinically, which should foster their clinical evaluation.