Emerging paradigms in cardiomyopathies associated with cancer therapies.
Emerging paradigms in cardiomyopathies associated with cancer therapies.
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DOI：
10.1161/circresaha.113.300218
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发表时间：
2013-08-30
影响因子：
20.1
通讯作者：
Moslehi JJ
中科院分区：
文献类型：
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作者：
Ky B;Vejpongsa P;Yeh ET;Force T;Moslehi JJ
癌症患者的心血管护理（“肿瘤学”）由于癌症治疗的最新进展已经成为临床医学中的新学科，并且由作为癌症治疗的直接结果而发生的心血管并发症驱动。传统的治疗方法，如蒽环类药物和放射治疗，多年来一直被认为有心血管并发症。较少预期的是“靶向”癌症治疗的心血管效应，最初认为这些治疗是针对癌细胞的，不会对心脏产生任何不良影响。癌症通常由蛋白激酶的突变、易位和/或过表达驱动。这些突变的激酶中的大多数是酪氨酸激酶，尽管丝氨酸/苏氨酸激酶在一些恶性肿瘤中也起关键作用。已经开发了几种针对这些激酶的药物，但还有更多的药物正在开发中。主要的成功主要局限于靶向Her 2（在乳腺癌中突变或过度表达）、BCR-ABL（CML和某些ALL病例）和c-Kit（胃肠道间质瘤）的药物。其他靶向更复杂的恶性肿瘤（如晚期实体瘤）的药物也取得了成功，但没有延长CML患者的生命。早在第一种靶向治疗药物出现的几年前，Judah Folkman就正确地提出，要解决实体瘤问题，必须靶向固有的新血管生成。不幸的是，新出现的证据证实，血管生成抑制剂引起心脏并发症，包括高血压，血栓形成和心力衰竭。第22章这就是陷阱另一方面，从这种靶向治疗中意外出现的心肌病可以提供对心脏正常功能的关键见解。
The cardiovascular care of cancer patients (“Cardio-Oncology”) has emerged as a new discipline in clinical medicine given recent advances in cancer therapy, and is driven by the cardiovascular complications that occur as a direct result of cancer therapy. Traditional therapies, such as anthracyclines and radiation, have been recognized for years to have cardiovascular complications. Less expected were the cardiovascular effects of “targeted” cancer therapies, which were initially felt to be specific to cancer cells and would spare any adverse effects on the heart. Cancers are typically driven by mutations, translocations, and/or over-expression of protein kinases. The majority of these mutated kinases are tyrosine kinases, though serine/threonine kinases also play key roles in some malignancies. Several agents were developed to target these kinases, but many more are in development. Major successes have been largely restricted to agents targeting Her2 (mutated or over-expressed in breast cancer), BCR-ABL (CML and some cases of ALL),and c-Kit (gastrointestinal stromal tumor).Other agents targeting more complex malignancies such as advanced solid tumors have had successes, but have not extended life to the degree seen with CML. Years before the first targeted therapeutic, Judah Folkman correctly proposed that to address solid tumors, one had to target the inherent neo-angiogenesis. Unfortunately, emerging evidence confirms that angiogenesis inhibitors cause cardiac complications, including hypertension, thrombosis, and heart failure. And therein lies the Catch 22. On the other hand, cardiomyopathies that arise unexpectedly from such targeted therapies can provide key insights into the normal function of the heart.