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Hypoxia and its Modification in Bladder Cancer: Current and Future Perspectives
Clinical Oncology ( IF 3.4 ) Pub Date : 2021-03-21 , DOI: 10.1016/j.clon.2021.03.001
T Lodhi 1 , Y P Song 1 , C West 2 , P Hoskin 3 , A Choudhury 4
Affiliation  

Radiotherapy plays an essential role in the curative treatment of muscle-invasive bladder cancer (MIBC). Hypoxia affects the response to MIBC radiotherapy, limiting radiocurability. Likewise, hypoxia influences MIBC genetic instability and malignant progression being associated with metastatic disease and a worse prognosis. Hypoxia identification in MIBC enables treatment stratification and the promise of improved survival. The most promising methods are histopathological markers such as necrosis; biomarkers of protein expression such as HIF-1α, GLUT-1 and CAIX; microRNAs; and novel mRNA signatures. Although hypoxia modification can take different forms, the gold standard remains carbogen and nicotinamide, which improve local control rates in bladder preservation and absolute overall survival with no significant increase in late toxicity. This is an exciting time for evolving therapies such as bioreductive agents, novel oxygen delivery techniques, immunotherapy and poly (ADP-ribose) polymerase 1 (PARP) inhibitors, all in development and representing upcoming trends in MIBC hypoxia modification. Whatever the future holds for hypoxia-modified radiotherapy, there is no doubt of its importance in MIBC. mRNA signatures provide an ideal platform for the selection of those with hypoxic tumours but are yet to qualified and integrated into the clinic. Future interventional trials will require biomarker stratification to ensure optimal treatment response to improve outcomes for patients with MIBC.



中文翻译:

膀胱癌的缺氧及其改变:当前和未来的前景

放射治疗在肌层浸润性膀胱癌 (MIBC) 的治愈性治疗中起着至关重要的作用。缺氧会影响对 MIBC 放射治疗的反应,从而限制放射治愈性。同样,缺氧会影响 MIBC 的遗传不稳定性和与转移性疾病和较差预后相关的恶性进展。MIBC 中的缺氧识别使治疗分层和提高生存率成为可能。最有前途的方法是组织病理学标记,例如坏死;蛋白质表达的生物标志物,如 HIF-1α、GLUT-1 和 CAIX;微RNA;和新的 mRNA 特征。虽然缺氧修饰可以采取不同的形式,但金标准仍然是碳原和烟酰胺,它们提高了膀胱保存的局部控制率和绝对总生存率,而晚期毒性没有显着增加。对于生物还原剂、新型氧输送技术、免疫疗法和聚(ADP-核糖)聚合酶 1 (PARP) 抑制剂等不断发展的疗法来说,这是一个激动人心的时刻,所有这些都在开发中,代表着 MIBC 缺氧修饰的即将到来的趋势。无论缺氧改良放疗的未来如何,它在 MIBC 中的重要性是毋庸置疑的。mRNA 特征为选择那些患有缺氧肿瘤但尚未合格并整合到临床中的患者提供了一个理想的平台。未来的介入试验将需要生物标志物分层,以确保最佳治疗反应,以改善 MIBC 患者的预后。一切都在发展中,代表着 MIBC 缺氧修饰的即将到来的趋势。无论缺氧改良放疗的未来如何,它在 MIBC 中的重要性是毋庸置疑的。mRNA 特征为选择那些患有缺氧肿瘤但尚未合格并整合到临床中的患者提供了一个理想的平台。未来的介入试验将需要生物标志物分层,以确保最佳治疗反应,以改善 MIBC 患者的预后。一切都在发展中,代表着 MIBC 缺氧修饰的即将到来的趋势。无论缺氧改良放疗的未来如何,它在 MIBC 中的重要性是毋庸置疑的。mRNA 特征为选择那些患有缺氧肿瘤但尚未合格并整合到临床中的患者提供了一个理想的平台。未来的介入试验将需要生物标志物分层,以确保最佳治疗反应,以改善 MIBC 患者的预后。

更新日期:2021-05-08
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