The role of lipid metabolism in cancer radioresistance

Radiotherapy is one of the main therapies for cancer. The process leading to radioresistance is still not fully understood. Cancer radiosensitivity is related to the DNA reparation of cancer cells and the tumor microenvironment (TME), which supports cancer cell survival. Factors that affect DNA reparation and the TME can directly or indirectly affect the radiosensitivity of cancer. Recent studies have shown that lipid metabolism in cancer cells, which is involved in the stability of cell membrane structure, energy supply and signal transduction of cancer cells, can also affect the phenotype and function of immune cells and stromal cells in the TME. In this review, we discussed the effects of lipid metabolism on the radiobiological characteristics of cancer cells and the TME. We also summarized recent advances in targeted lipid metabolism as a radiosensitizer and discussed how these scientific findings could be translated into clinical practice to improve the radiosensitivity of cancer (AU)

PARP inhibitor niraparib as a radiosensitizer promotes antitumor immunity of radiotherapy in EGFR-mutated non-small cell lung cancer

Background Poly-(ADP-Ribose)-Polymerase inhibitors (PARPi) were reported as radiosensitizers in non-small cell lung cancer (NSCLC) with wide-type epidermal growth factor receptor (EGFR), but the effects of radiation combined with PARPi were not investigated in EGFR-mutated NSCLC. Moreover, the underlying mechanisms were not well examined. This study aimed to study the efficacy of radiation combined with niraparib in EGFR-mutated NSCLC and explore their influence on the immune system. Methods Clone formation and apoptosis assay were conducted to explore the effects of niraparib and radiation. Immunofluorescence was conducted to detect the double-strand DNA breaks. Real-time PCR and immunoblotting were employed to evaluate the activation of STING/TBK1/TRF3 pathway and the expression levels of interferon β, CCL5 and CXCL10. Immunocompetent mice model bearing with subcutaneous Lewis lung cancer was established to confirm the results in vivo. Results Niraparib and radiation were synergistic to inhibit tumor both in vitro and in vivo. Radiation plus niraparib could activate anti-tumor immunity, which appeared as increased CD8+ T lymphocytes and activated STING/TBK1/IRF3 pathway. Conclusion PARPi not only as a radiosensitizer inhibited EGFR-mutated NSCLC tumor growth, but also cooperated with radiation to promote anti-tumor immune responses (AU)

Concurrent radiotherapy with S-1 plus cisplatin versus concurrent radiotherapy with cisplatin alone for the treatment of locally advanced cervical carcinoma: a pilot randomised controlled trial

Background: In the present study, we compared the efficacy and safety of concurrent radiotherapy with S-1 plus cisplatin (CRSC) versus concurrent radiotherapy with cisplatin alone (CRC) for the treatment of advanced cervical carcinoma (ACC). Methods: Between February 2006 and January 2009, 72 eligible patients with ACC were included and randomly divided into two groups. Thirty-six patients received CRSC with radiotherapy (60 Gy/30 fractions over 6 weeks) beginning on day 1, S-1 (according to body surface area) for 28 days repeated every 6 weeks, and cisplatin (50 mg/ m2, intravenously on day 1) every 4 weeks for two cycles. The other 36 received CRC at the same cisplatin and radiotherapy dosage as for CRSC. The primary outcome was overall survival, whereas the secondary outcomes included progression-free survival and toxicity. Results: The median overall survival was 75 months (range 4-86 months) for the CRSC group and 66 months (range 3-87 months) for the CRC group (P = 0.039). The median corresponding progression-free survival was 66 months (range 3-75 months) and 58 months (range 3-71 months), respectively (P = 0.042). The toxicity profile was similar in both the groups. Conclusion: Our results suggested that CRSC might be more effective than CRC in patients with ACC with acceptable toxicity (AU)

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Radiosensitization by gold nanoparticles

Recent years brought increasing use of gold nano particles (GNP) as a model platform for interaction of irradiation and GNPs aiming radiosensitization. Endocytosis seems to be one of the major pathways for cellular uptake of GNPs. Internalization mechanism of GNPs is likely receptor-mediated endocytosis, influenced by GNP size, shape, its coating and surface charging. Many showed that DNA damage can occur as a consequence of metal-enhanced production of low energy electrons, Auger electrons and alike. Kilovoltage radiotherapy (RT) carries significantly higher dose enhancement factor (DEF) that is observed with megavoltage irradiations, the latter usually been at the order of 1.1-1.2. Higher gold concentrations seem to carry higher risk of toxicity, while with lower concentrations the DEF can be reduced. Adding a chemotherapeutic agent could increase level of enhancement. Clinical trials are eagerly awaited with a promise of gaining more knowledge deemed necessary for more successful transition to widespread clinical practice (AU)

Preliminary clinical study of weekly recombinant human endostatin as a hypoxic tumour cell radiosensitiser combined with radiotherapy in the treatment of NSCLCP

OBJECTIVE: To investigate the clinical effects and adverse effects of weekly recombinant human endostatin (RHES) as a hypoxic tumour cell radiosensitiser combined with radiotherapy in the treatment of non-small-cell lung cancer (NSCLC). METHODS: Fifty hypoxia-positive cases of pathology-diagnosed NSCLC (stage I-III) were randomly divided into a RHES+radiotherapy group (25 cases) and a radiotherapy alone group (25 cases). Intensity-modulated radiotherapy (IMRT) with a total dose of 60 Gy/30F/6W was adopted in the two groups. Target area included primary foci and metastatic lymph nodes. In the RHES+radiotherapy group, RHES (15 mg/day) was intravenously given during the first week. The therapeutic effects and adverse reactions were evaluated after treatment. RESULTS: In the RHES+radiotherapy and radiotherapy alone groups, the total effective rates (CR+PR) were 80% and 44% (χ(2)=6.87, p=0.009), respectively. The one-year and two-year local control rates were (78.9±8.4)% and (68.1±7.8)% (p=0.027), and (63.6±7.2)% and (43.4±5.7)% (p=0.022), respectively. The median progression-free survival was (21.1±0.97) and (16.5±0.95) months, respectively. The one-year and two-year overall survival rates were (83.3±7.2)% and (76.6±9.3)% (p=0.247), and (46.3±2.4)% and (37.6±9.1)% (p=0.218), respectively. CONCLUSION: RHES combined with radiotherapy within the first week has better short-term therapeutic effects and local control rate, and no severe adverse reactions in treatment of NSCLC. However, it failed to significantly improve the one-year and two-year overall survival rates (AU)

Fármacos activos en sistema nervioso central con utilidad radiosensibilizante

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RT paliativa y RT conformacional. Indicaciones, resultados y perspectivas frente a la asociación

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Fluoropirimidinas y radioterapia en cáncer gastrointestinal / Fluoropyrimidines and radiotherapy in gastrointestinalcancer

Las fluoropirimidinas son unos fármacos antineoplásicos cuya estructura química es similar a la de diversos sustratos imprescindibles en la síntesis de los ácidos nucleicos. Entre ellas destaca el 5-fluorouracilo (5-FU), una pirimidina fluorada que actúa como falso nucleótido. Diversos estudios experimentales han demostrado que la asociación de 5-FU y radioterapia aumenta la citotoxicidad de ésta, aunque el mecanismo de dicha radiopotenciación aun no es bien conocido. En este trabajo revisamos las principales características de las fluoropirimidinas, y recogemos los estudios más relevantes sobre el uso de 5-FU en asociación con radioterapia para el tratamiento de los tumores gastrointestinales (AU)

Radioterapia y citoprotección. Mecanismo de acción. Bases

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