(chemo)radiotherapy

Overview

(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.

Focus of Latest Publications

Recent research has explored radiotherapy approaches across multiple cancer types, with emphasis on optimizing patient selection and treatment sequencing. In early nodal breast cancer, a prospective registry study (RAPCHEM) examined radiotherapy tailored to nodal response after primary chemotherapy, demonstrating excellent locoregional control and providing updated 10-year follow-up data. For older women with stage I hormone receptor-positive breast cancer, the role and necessity of postoperative radiotherapy continues to be investigated as clinicians weigh competing evidence on treatment efficacy.

Advanced radiotherapy modalities and combination strategies are expanding treatment options beyond conventional photon therapy. Proton beam therapy (PBT) has emerged as an alternative to conventional photon therapy for locally advanced pancreatic cancer, evaluated in combination with chemotherapy. Novel combination approaches include hyperthermia-enhanced radiotherapy, where stretchable hyperthermia patches demonstrated substantial synergy with radiotherapy in nasopharyngeal carcinoma, reducing clonogenic cell survival by over 54%, elevating apoptosis by 90%, and enhancing tumor control in vivo. Additionally, immuno-oncology combinations are being investigated, including neoadjuvant tislelizumab (anti-PD-L1 monoclonal antibody) plus chemoradiotherapy for resectable esophageal squamous cell carcinoma, and anlotinib combined with radiotherapy for glioblastoma, particularly in patients with unmethylated MGMT who derive minimal benefit from standard temozolomide chemoradiotherapy.

Understanding and overcoming resistance mechanisms is critical for improving radiotherapy efficacy. Mechanistic studies in cholangiocarcinoma revealed that H3K4 methylation-driven upregulation of Calbindin 2 (CALB2) promotes both immune evasion and chemoradiotherapy resistance through a signaling axis involving Keratin 7 (KRT7) and PD-L1 that impairs T cell activation. CALB2 silencing significantly sensitized cholangiocarcinoma tumors to gemcitabine plus radiotherapy, suggesting that targeting this epigenetic mechanism may overcome resistance to combined modality therapy.

Emerging preclinical models are advancing our capacity to predict radiotherapy response and study tumor microenvironment interactions. Complex cerebral organoids incorporating vasculature and microglial cells successfully modeled glioblastoma behavior and radiotherapy response, demonstrating vascular co-option and reprogramming of microglia into tumor-associated macrophages, with analysis of tumor recurrence following radiotherapy. Such models provide platforms to investigate mechanisms of therapy resistance and inform development of more effective therapeutic strategies.

Key Publications

• NEWJul Non-secretory Multiple Myeloma: A Challenge to Diagnose. (Mymensingh medical journal : MMJ, 2026, PMID 42375076): "He is currently being treated with chemotherapy and has already shown improvement."
• NEWJul Tailoring radiotherapy in cT1-2N1 breast cancer to nodal response on primary chemotherapy (RAPCHEM: BOOG 2010-03): 10-year follow-up results of a Dutch, prospective, registry study. (The Lancet. Oncology, 2026, PMID 42372742): "Here, we present 10-year results."
• NEWJul Potential Role of Proton Beam Therapy for Locally Advanced Pancreatic Cancer. (Anticancer research, 2026, PMID 42373264): "This study evaluated the outcomes and adverse events of PBT combined with chemotherapy in LAPC, with outcomes of chemotherapy alone presented for reference."
• NEWJul Postoperative anlotinib plus radiotherapy in patients with newly diagnosed, unmethylated O6-methylguanine-DNA methyltransferase glioblastoma: A single-arm, phase 2 study. (Cancer, 2026, PMID 42339996): "The objective of this phase 2 study was to evaluate the efficacy of anlotinib plus radiotherapy in this disease."
• NEWJun Modeling, Analysis, and Optimal Control of Leukemic Cell Population Dynamics Under Therapy. (Bulletin of mathematical biology, 2026, PMID 42342915): "This extension aims to provide a more refined mathematical basis for investigating anti-cancer strategies."
• NEWJul Mortality in Castration Resistant Prostate Cancer Patients With and Without Pre-Existing Cardiovascular Disease Receiving Oral Androgen Receptor Pathway Inhibitors. (Pharmacoepidemiology and drug safety, 2026, PMID 42322109): "...receiving ARPi compared to chemotherapy."
• NEWJan Nanomedicine-Based Therapeutic Approaches in Colorectal Cancer Using Patient-Derived Xenograft Models: Prospects and Challenges. (International journal of nanomedicine, 2026, PMID 42311426): "A range of nanocarrier systems, including nanoparticles, liposomes, and dendrimers, have been explored for delivery of chemotherapeutic agents, biologics, and small-molecule inhibitors, demonstrating improved tumor targeting and therapeutic potential."
• NEWJun Patient-derived organoids for personalized drug response profiling and multi-omics integration in oral squamous cell carcinoma. (iScience, 2026, PMID 42305621): "These PDOs recapitulated clinical chemotherapy response diversity."
• May Value-based pricing of tislelizumab plus chemotherapy versus chemotherapy alone for advanced oesophageal squamous cell carcinoma: a Markov modelling study from the US payer perspective. (BMJ open, 2026, PMID 42203284): "This study aimed to determine the value-based price range at which tislelizumab combined with chemotherapy becomes cost-effective compared with chemotherapy alone for treating advanced oesophageal squamous cell carcinoma."
• May International practice patterns and perceptions of pressurised intraperitoneal aerosol chemotherapy for management of gastric cancer: A global clinician survey. (European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 2026, PMID 42173034): "...particularly with respect to patient selection, chemotherapy regimens, and response assessment."