Pharmacological strategies to spare normal tissues from radiation damage: useless or overlooked therapeutics?
Half of all the patients with a solid malignant tumor will receive radiation therapy (RT) with a curative or palliative intent during the course of their treatment. Deleterious effects may result in acute and chronic toxicities that reduce the long-term health-related quality of life of these patients. High-tech RT enables precise beam delivery that conforms closely to the shape of tumors yielding an improved efficacy/toxicity ratio. However, sophisticated RT will not completely prevent toxicity in the irradiated field, especially as normal tissue constraints are offset by dose escalation or concurrent chemotherapy. Pharmacological agents can be used before or after RT to reduce side effects and are classified based on the timing of RT delivery. "Radioprotectors," used as a molecular prophylactic strategy before RT, are mostly based on antioxidant properties. Currently, amifostine is the only radioprotector approved for use in the clinic. "Mitigators," given during or shortly after RT, reduce the action of cellular ionizing radiation on normal tissues before the emergence of symptoms. Lastly, a "treatment" is the administration of an agent once symptoms have developed in order to reverse those that are mostly due to fibrosis. This review presents the major known physiopathological mechanisms involved in radiation response and tissue damage for which potential pharmacological candidates are emerging. We discuss the potential clinical relevance of such therapeutics in the era of high-precision radiotherapy.
Inserm U1030, Radiothérapie moléculaire, Université Paris XI, le Kremlin-Bicêtre, France. bourgier@igr.fr
Céline
C
Bourgier
Antonin
A
Levy
Marie-Catherine
MC
Vozenin
Eric
E
Deutsch
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002097:C-Reactive Protein / Q000502:physiology; D004260:DNA Repair; D005355:Fibrosis; D006801:Humans; D016328:NF-kappa B / Q000502:physiology; D009369:Neoplasms / Q000532:radiotherapy*; D010743:Phospholipids / Q000502:physiology; D011832:Radiation Injuries / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D011878:Radiotherapy / Q000009:adverse effects; D000683:Serum Amyloid P-Component / Q000502:physiology; D013108:Sphingomyelin Phosphodiesterase / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000502:physiology; D000099153:Pentraxins
D000975:Antioxidants; D002097:C-Reactive Protein; D016328:NF-kappa B; D010743:Phospholipids; D011837:Radiation-Protective Agents; D000683:Serum Amyloid P-Component; D013108:Sphingomyelin Phosphodiesterase; D053773:Transforming Growth Factor beta1; D000099153:Pentraxins