Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.

The N6-methyladenosine (M6A) modification is the most common internal chemical modification of RNA molecules in eukaryotes. This modification can affect mRNA metabolism, regulate RNA transcription, nuclear export, splicing, degradation, and translation, and significantly impact various aspects of physiology and pathobiology. Radiotherapy is the most common method of tumor treatment. Different intrinsic cellular mechanisms affect the response of cells to ionizing radiation (IR) and the effectiveness of cancer radiotherapy. In this review, we summarize and discuss recent advances in understanding the roles and mechanisms of RNA M6A methylation in cellular responses to radiation-induced DNA damage and in determining the outcomes of cancer radiotherapy. Insights into RNA M6A methylation in radiation biology may facilitate the improvement of therapeutic strategies for cancer radiotherapy and radioprotection of normal tissues.

Radiotherapy (RT) triggers immunogenic cell death (ICD). L-ASNase, which catalyzes the conversion of asparagine (Asn), thereby depleting it, is used in the treatment of blood cancers. In previous work, we showed that CRT3LP and CRT4LP, PASylated L-ASNases conjugated to the calreticulin (CRT)-specific monobodies CRT3 and CRT4, increase the efficacy of ICD-inducing chemotherapy. Here, we assessed their efficacy in tumor-bearing mice treated with RT. Methods: Monobody binding was evaluated by in silico molecular docking analysis. The expression and cellular localization of ecto-CRT were assessed by confocal imaging and flow cytometry. The antitumor effect and the roles of CRT3LP and CRT4LP in irradiation (IR)-induced ICD in tumors were analyzed by ELISA, immunohistochemistry, and immune analysis methods. Results: Molecular docking analysis showed that CRT3 and CRT4 monobodies were stably bound to CRT. Exposure to 10 Gy IR decreased the viability of CT-26 and MC-38 tumor cells in a time-dependent manner until 72 h, and increased the expression of the ICD marker ecto-CRT (CRT exposed on the cell surface) and the immune checkpoint marker PD-L1 until 48 h. IR enhanced the cytotoxicity of CRT3LP and CRT4LP in CT-26 and MC-38 tumor cells, and increased reactive oxygen species (ROS) levels. In mice bearing CT-26 and MC-38 subcutaneous tumors treated with 6 Gy IR, Rluc8-conjugated CRT-specific monobodies (CRT3-Rluc8 and CRT4-Rluc8) specifically targeted tumor tissues, and CRT3LP and CRT4LP increased total ROS levels in tumor tissues, thereby enhancing the antitumor efficacy of RT. Tumor tissues from these mice showed increased mature dendritic, CD4+ T, and CD8+ T cells and pro-inflammatory cytokines (IFNγ and TNFα) and decreased regulatory T cells, and the expression of tumor cell proliferation markers (Ki67 and CD31) was downregulated. These data indicate that the combination of IR and CRT-targeting L-ASNases activated and reprogramed the immune system of the tumor microenvironment. Consistent with these data, an immune checkpoint inhibitor (anti-PD-L1 antibody) markedly increased the therapeutic efficacy of combined IR and CRT-targeting L-ASNases. Conclusion: CRT-specific L-ASNases are useful as additive drug candidates in tumors treated with RT, and combination treatment with anti-PD-L1 antibody increases their therapeutic efficacy.

Cancer radiopharmaceutical therapies (RPTs) have demonstrated great promise in the treatment of neuroendocrine and prostate cancer, giving hope to late-stage metastatic cancer patients with currently very few treatment options. These therapies have sparked a large amount of interest in pre-clinical research due to their ability to target metastatic disease, with many research efforts focused towards developing and evaluating targeted RPTs for different cancer types in in vivo models. Here we describe a method for monitoring real-time in vivo binding kinetics for the pre-clinical evaluation of cancer RPTs. Recognizing the significant heterogeneity in biodistribution of RPTs among even genetically identical animal models, this approach offers long-term monitoring of the same in vivo organism without euthanasia in contrast to ex vivo tissue dosimetry, while providing high temporal resolution with a low-cost, easily assembled platform, that is not present in small-animal SPECT/CTs. The method utilizes the developed optical fiber-based γ-photon biosensor, characterized to have a wide linear dynamic range with Lutetium-177 (177Lu) activity (0.5-500 μCi/mL), a common radioisotope used in cancer RPT. The probe\'s ability to track in vivo uptake relative to SPECT/CT and ex vivo dosimetry techniques was verified by administering 177Lu-PSMA-617 to mouse models bearing human prostate cancer tumors (PC3-PIP, PC3-flu). With this method for monitoring RPT uptake, it is possible to evaluate changes in tissue uptake at temporal resolutions <1 min to determine RPT biodistribution in pre-clinical models and better understand dose relationships with tumor ablation, toxicity, and recurrence when attempting to move therapies towards clinical trial validation.

Cervical cancer is one of the most frequent gynecological malignancies in Brazil, and most of the patients require pelvic radiotherapy as part of oncological treatment. Pelvic radiotherapy induces ovarian premature insufficiency in pre-menopausal women. This condition impacts the life quality and increases the risk of osteoporosis, obesity, cardiovascular, and neurodegenerative diseases in the middle and long term. Most of these patients have no access to hormonal replacement therapy. Techniques such as ovarian transposition have questionable results when aiming to preserve ovarian function. In this context, a promising alternative is the implantation of fresh ovarian tissue, outside the radiotherapy field, in the abdominal cavity (orthotopic implantation) or in other sites such as the forearm, breast, or subcutaneous tissue (heterotopic implantation). Here we report a successful case of autologous implantation of fresh ovarian tissue in the inner thigh of a young patient with advanced cervical cancer, who was a candidate for concurrent chemoradiotherapy.

Fractional calculus has recently been applied to the mathematical modelling of tumour growth, but its use introduces complexities that may not be warranted. Mathematical modelling with differential equations is a standard approach to study and predict treatment outcomes for population-level and patient-specific responses. Here, we use patient data of radiation-treated tumours to discuss the benefits and limitations of introducing fractional derivatives into three standard models of tumour growth. The fractional derivative introduces a history-dependence into the growth function, which requires a continuous death-rate term for radiation treatment. This newly proposed radiation-induced death-rate term improves computational efficiency in both ordinary and fractional derivative models. This computational speed-up will benefit common simulation tasks such as model parameterization and the construction and running of virtual clinical trials.

Angiosarcomas are a rare subtype of sarcomas originating from vascular endothelial cells. Though frequently found in the head and neck area, there are minimal reports of radiation-induced angiosarcomas in this area. They have a poor prognosis due to a high rate of lymph node metastasis and, hence, require to be addressed promptly in order to improve survival. We present a rare case of radiation-induced angiosarcoma in a patient previously irradiated for squamous cell carcinoma of the neck. Due to variable and complex patient presentations of the disease, this case will help raise awareness of an uncommon complication of a common treatment offered to patients.

Intracellular transcytosis can enhance the penetration of nanomedicines to deep avascular tumor tissues, but strategies that can improve transcytosis are limited. In this study, we discovered that pyknomorphic extracellular matrix (ECM) is a shield that impairs endocytosis of nanoparticles and their movement between adjacent cells and thus limits their active transcytosis in tumors. We further showed that degradation of pivotal constituent of ECM (i.e., collagen) effectively enhances intracellular transcytosis of nanoparticles. Specifically, a collagenase conjugating transcytosis nanoparticle (Col-TNP) can dissociate into collagenase and cationized gold nanoparticles in response to tumor acidity, which enables their ECM tampering ability and active transcytosis in tumors. The breakage of ECM further enhances the active transcytosis of cationized nanoparticles into deep tumor tissues as well as radiosensitization efficacy of pancreatic adenocarcinoma. Our study opens up new paths to enhance the active transcytosis of nanomedicines for the treatment of cancers and other diseases.

Radiotherapy (RT), as one of the main methods of clinical tumor treatment, has been applied to the treatment of most solid tumors. However, the effect of RT is compromised by the radiation resistance of tumor hypoxic environment and non-specific damage caused by high-dose radiation. Bismuth chalcogenides (Bi2X3, X = S, Se) based nanodrugs have attracted widespread attention as highly efficient radiosensitizers due to their high photoelectric effect and excellent biocompatibility. More importantly, specially designed nanocomposites can effectively alleviate the radiation resistance of tumor tissues. Here, for the first time, we systematically summarize the latest progresses of Bi2X3 nanodrugs to enhance RT by alleviating the hypoxic tumor microenvironment. These emerging Bi2X3 nanodrugs mainly include three aspects, which are Bi2X3 nanocomposites with high-efficient O2 supply, non-O2-dependent Bi2X3 nanocomposites RT enhancers, and Bi2X3 nanocomposites-based photothermal-enhanced radiosensitizers. These Bi2X3 nanodrugs can effectively overcome the RT resistance of tumor hypoxic microenvironment, and have extremely high therapeutic effects and clinical application prospects. Finally, we put forward the challenges and prospects of Bi2X3 nanomaterials in the field of RT.

BACKGROUND: Secondary lymphedema is a leading sequela of cancer surgery and radiotherapy. The microsurgical transfer of lymph node flaps (LNFs) to affected limbs can improve the symptoms. The intra-abdominal cavity contains an abundant heterogenic source. The aim of this study is to aid selection among intra-abdominal LNFs.
METHODS: Eight LNFs were harvested in a microsurgical fashion at five sites in 16 cadavers: gastroepiploic, jejunal, ileal, ileocolic, and appendicular. These flaps were compared regarding size, weight, arterial diameter, and lymph node (LN) count after histologic verification.
RESULTS: One hundred and sixteen flaps were harvested. The exposed area correlated with the flap weight and volume (r2  = 0.86, r = 0.9). While gastroepiploic LNFs (geLNFs) showed the highest median weight of 99 ml, the jejunal LNFs (jLNFs) had the highest density with 3.8 LNs per 10 ml. The most reliable jLNF was 60 cm from the ligament of Treitz. Three or more LNs were contained in 94% of the jejunal, 88% of the ileal/ileocolic, and 63% of the omental LNs. The ileocolic LNF had the largest arterial diameter of 3 mm, yet the smallest volume.
CONCLUSIONS: jLNF and ileal LNF provide a reliable, high LN density for simultaneous, smaller recipient sites. geLNFs are more suitable for larger recipient sites.