(chemo)radiotherapy

(Chemo)Radiotherapy — encompassing both radiotherapy (RT) alone and chemoradiotherapy (CRT), in which ionizing radiation is combined with systemic chemotherapeutic agents — represents one of the foundational pillars of modern oncological treatment. Radiotherapy leverages high-energy ionizing radiation to induce DNA double-strand breaks, disrupt cellular replication, and drive tumor cell death, while the concurrent or sequential addition of chemotherapy agents (chemoradiotherapy) exploits pharmacological radiosensitization to enhance tumor cell kill beyond what either modality achieves independently. The biological rationale for combining these modalities includes spatial cooperation (chemotherapy targeting distant micrometastases while radiation controls the locoregional disease), temporal cooperation (chemotherapy sensitizing cells to radiation-induced damage), and the exploitation of complementary mechanisms of DNA damage and repair inhibition. (Chemo)Radiotherapy is applied across an exceptionally broad range of malignancies — including head and neck cancers, esophageal squamous cell carcinoma, cervical cancer, diffuse intrinsic pontine glioma, rectal cancer, breast cancer, and prostate cancer — where it functions as a definitive, neoadjuvant, adjuvant, or palliative treatment depending on disease stage and patient factors.

The efficacy of (chemo)Radiotherapy is governed by complex tumor biology, including the capacity of cancer cells to repair radiation-induced DNA damage via pathways such as homologous recombination (HR) and the Shieldin complex, the oxygenation status of the tumor microenvironment, and the molecular landscape of the tumor. Resistance to radiotherapy — radioresistance — remains a critical clinical challenge and is an active focus of translational research, with investigators identifying specific molecular targets such as EZH2, Pol θ (theta), and mitochondrial RNA polymerase as candidate vulnerabilities. Parallel efforts focus on radiosensitization strategies employing small molecules, natural compounds, nanoparticle delivery systems, and emerging physical modalities such as hyperthermia patches.