Adverse reactions to targeted and non-targeted chemotherapeutic drugs with emphasis on hypersensitivity responses and the invasive metastatic switch.
Adverse reactions to targeted and non-targeted chemotherapeutic drugs with emphasis on hypersensitivity responses and the invasive metastatic switch.
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DOI：
10.1007/s10555-013-9447-3
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发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Pham NH
中科院分区：
文献类型：
--
作者：
Baldo BA;Pham NH
100多种药物被用于治疗多种不同的癌症。它们可分为相对广泛、非靶向特异性的药物以及基于对个体癌症更精细的了解而开发的靶向药物，这些靶向药物针对不同癌细胞上的特定分子靶点。这两类中的单个药物根据其杀伤癌细胞的作用机制进行了分类。靶向药物包括蛋白酶体抑制剂、毒性嵌合蛋白以及信号转导抑制剂，如酪氨酸激酶（非受体和受体）、丝氨酸/苏氨酸激酶、组蛋白去乙酰化酶和哺乳动物雷帕霉素靶蛋白抑制剂。日益广泛使用的靶向血管（血管内皮生长因子）和血小板衍生内皮生长因子阻断可引发一系列病理后果。许多非靶向药物具有细胞毒性，会抑制造血功能，并引发皮疹以及血管、肺和肝损伤。靶向药物的细胞毒性副作用发生频率较低，通常严重程度也较低，但它们有自身不寻常的不良反应，例如包括QT间期延长、特征性的丘疹脓疱性皮疹、指甲疾病和手足皮肤反应变体。超敏反应这一术语在多个学科中广泛使用，但人们脑海中的定义并不总是相同，术语需要标准化。这在癌症化疗中尤为明显，在癌症化疗中，抗肿瘤药物诱导的血小板减少、中性粒细胞减少、贫血、血管疾病、肝损伤和肺部疾病以及许多皮肤表现有时具有免疫基础。然而，靶向治疗所有不良后果中最隐匿的是肿瘤适应、恶性程度增加以及使用抑制血管内皮生长因子 - A通路的抗血管生成药物时出现的侵袭性转移转换。本文介绍了44种非靶向和33种靶向的常用化疗药物的不良反应，并讨论了诊断、预处理、脱敏以及理解各种药物诱导反应的潜在机制的重要性。需要广泛接受超敏反应的构成，并让过敏专科医生更多地参与化疗药物诱导的超敏反应的诊断、治疗和预防。
More than 100 drugs are used to treat the many different cancers. They can be divided into agents with relatively broad, non-targeted specificity and targeted drugs developed on the basis of a more refined understanding of individual cancers and directed at specific molecular targets on different cancer cells. Individual drugs in both groups have been classified on the basis of their mechanism of action in killing cancer cells. The targeted drugs include proteasome inhibitors, toxic chimeric proteins and signal transduction inhibitors such as tyrosine kinase (non-receptor and receptor), serine/threonine kinase, histone deacetylase and mammalian target of rapamycin inhibitors. Increasingly used targeted vascular (VEGF) and platelet-derived endothelial growth factor blockade can provoke a range of pathological consequences. Many of the non-targeted drugs are cytotoxic, suppressing haematopoiesis as well as provoking cutaneous eruptions and vascular, lung and liver injury. Cytotoxic side effects of the targeted drugs occur less often and usually with less severity, but they show their own unusual adverse effects including, for example, a lengthened QT interval, a characteristic papulopustular rash, nail disorders and a hand–foot skin reaction variant. The term hypersensitivity is widely used across a number of disciplines but not always with the same definition in mind, and the terminology needs to be standardised. This is particularly apparent in cancer chemotherapy where anti-neoplastic drug-induced thrombocytopenia, neutropenia, anaemia, vascular disorders, liver injury and lung disease as well as many dermatological manifestations sometimes have an immune basis. The most insidious of all adverse consequences of targeted therapies, however, are tumour adaptation, increased malignancy and the invasive metastatic switch seen with anti-angiogenic drugs that inhibit the VEGF-A pathway. Adverse reactions to 44 non-targeted and 33 targeted, frequently used, chemotherapeutic drugs are presented together with discussions of diagnosis, premedications, desensitizations and importance of understanding the mechanisms underlying the various drug-induced reactions. There is need for wide-ranging acceptance of what constitutes a hypersensitivity reaction and for allergists to be more involved in the diagnosis, treatment and prevention of chemotherapeutic drug-induced hypersensitivity reactions.
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影响因子：
1.1
作者：
Brehler, R;Reimann, S;Metze, D
通讯作者：
Metze, D
DOI：
10.1038/nrc2442
发表时间：
2008-08
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1111/j.1538-7836.2012.04664.x
发表时间：
2012-04-01
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Arnold, D M;Santoso, S;Greinacher, A
通讯作者：
Greinacher, A
影响因子：
6.5
作者：
Borthakur, Gautam;O'Brien, Susan;Keating, Michael J.
通讯作者：
Keating, Michael J.
影响因子：
3.8
作者：
Adams, David H.;Ju, Cynthia;Jaeschke, Hartmut
通讯作者：
Jaeschke, Hartmut