Hypoxia and anemia: Factors in decreased sensitivity to radiation therapy and chemotherapy?
Hypoxia and anemia: Factors in decreased sensitivity to radiation therapy and chemotherapy?
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DOI：
10.1634/theoncologist.9-90005-31
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发表时间：
2004-01-01
期刊：
影响因子：
5.8
通讯作者：
Blackwell, K
中科院分区：
文献类型：
--
作者：
Harrison, L;Blackwell, K
缺氧是实体瘤的一个常见特征，发生在多种恶性肿瘤中。缺氧和贫血（导致肿瘤缺氧）可通过剥夺肿瘤细胞对这些药物的细胞毒活性所必需的氧气而导致电离辐射和化疗耐药。缺氧还可能通过一种或多种间接机制（包括蛋白质组和基因组变化）降低肿瘤对放射治疗和化疗的敏感性。这些效应反过来会导致侵袭性和转移潜力增加、细胞凋亡丧失和血管生成混乱，从而进一步增加治疗耐药性。对治疗前肿瘤氧合状态的预后意义的研究表明，缺氧（氧张力 [pO(2)] 值小于或等于 10 mmHg）与头颈癌、宫颈癌和软组织肉瘤的总体生存率和无病生存率较低、复发率较高以及局部控制较差相关。鉴于缺氧对标准癌症治疗的有害影响，人们研究了多种针对缺氧和贫血的靶向疗法，以努力提高治疗效果和患者预后。来自实验和临床研究的早期证据表明，重组人促红细胞生成素 (rHuEPO) 的施用可以通过增加血红蛋白水平并改善患有疾病或治疗相关贫血的患者的贫血来增强放射治疗和化疗的有效性。然而，在缺氧相关的治疗抵抗及其逆转领域还需要进一步研究。
Hypoxia is a common feature of solid tumors that occurs across a wide variety of malignancies. Hypoxia and anemia (which contributes to tumor hypoxia) can lead to ionizing radiation and chemotherapy resistance by depriving tumor cells of the oxygen essential for the cytotoxic activities of these agents. Hypoxia may also reduce tumor sensitivity to radiation therapy and chemotherapy through one or more indirect mechanisms that include proteomic and genomic changes. These effects, in turn, can lead to increased invasiveness and metastatic potential, loss of apoptosis, and chaotic angiogenesis, thereby further increasing treatment resistance. Investigations of the prognostic significance of pretreatment tumor oxygenation status have shown that hypoxia (oxygen tension [pO(2)] value less than or equal to10 mmHg) is associated with lower overall and disease-free survival, greater recurrence, and less locoregional control in head and neck carcinoma, cervical carcinoma, and soft-tissue sarcoma. In view of the deleterious effect of hypoxia on standard cancer treatment, a variety of hypoxia- and anemia-targeted therapies have been studied in an effort to improve therapeutic effectiveness and patient outcomes. Early evidence from experimental and clinical studies suggests the administration of recombinant human erythropoietin (rHuEPO) may enhance the effectiveness of radiation therapy and chemotherapy by increasing hemoglobin levels and ameliorating anemia in patients with disease- or treatment-related anemia. However, further research is needed in the area of hypoxia-related treatment resistance and its reversal.