Carbon Ions for Hypoxic Tumors: Are We Making the Most of Them?

SIMPLE SUMMARY: Carbon-ion radiotherapy is a potential elective treatment option for hypoxic tumors. Its high linear energy transfer enables enhanced cell killing in radiation-resistant tumors, while the Bragg peak ensures precise targeting. Clinical evidence in pancreatic and cervical cancers supports positive outcomes of carbon treatments. However, the power of carbon ions against tumor hypoxia is generally underexploited and should be considered to improve the clinical benefit. ABSTRACT: Hypoxia, which is associated with abnormal vessel growth, is a characteristic feature of many solid tumors that increases their metastatic potential and resistance to radiotherapy. Carbon-ion radiation therapy, either alone or in combination with other treatments, is one of the most promising treatments for hypoxic tumors because the oxygen enhancement ratio decreases with increasing particle LET. Nevertheless, current clinical practice does not yet fully benefit from the use of carbon ions to tackle hypoxia. Here, we provide an overview of the existing experimental and clinical evidence supporting the efficacy of C-ion radiotherapy in overcoming hypoxia-induced radioresistance, followed by a discussion of the strategies proposed to enhance it, including different approaches to maximize LET in the tumors.