History of the development of arsenic derivatives in cancer therapy
History of the development of arsenic derivatives in cancer therapy
复制标题
DOI：
10.1634/theoncologist.6-suppl_2-3
复制
发表时间：
2001-01-01
期刊：
影响因子：
5.8
通讯作者：
Anderson, KC
中科院分区：
文献类型：
--
作者：
Waxman, S;Anderson, KC
砷是一种天然物质，已被用于医学超过2,400年。在19世纪，它是本草学的中流砥柱。从18世纪到世纪，亚砷酸钾溶液（福勒氏溶液）被用于治疗各种全身性疾病。这种多用途溶液也是治疗慢性粒细胞白血病的主要疗法，直到被放射性酸细胞毒性化疗取代。在过去的100年里，砷的使用急剧下降，到20世纪90年代中期，唯一公认的适应症是治疗锥虫病。这种下降主要是由于对长期服用砷的毒性和潜在致癌性的担忧。砷治疗的重生发生在20世纪70年代，当时中国的医生开始使用三氧化二砷作为急性早幼粒细胞白血病（APL）治疗的一部分。他们积累的经验表明，静脉输注稳定的三氧化二砷溶液对新诊断的APL白血病患者和难治性和复发性APL患者都是非常安全和有效的。砷衍生物在这种疾病和其他恶性肿瘤中的作用机制有很多，包括诱导细胞凋亡、部分细胞分化、抑制增殖和抑制血管生成。分子生物学研究和正在进行的临床试验表明，三氧化二砷作为一种化疗药物，在恶性疾病的治疗中显示出巨大的前景。
Arsenic is a natural substance that has been used medicinally for over 2,400 years. In the 19th century, it was the mainstay of the materia medica. A solution of potassium arsenite (Fowler's solution) was used for a variety of systemic illnesses from the 18th until the 20th century. This multipurpose solution was also primary therapy for the treatment of chronic myelogenous leukemia until replaced by radiation acid cytotoxic chemotherapy. The past 100 years have seen a precipitous decline in arsenic use and, by the mid-1990s, the only recognized indication was the treatment of trypanosomiasis. Much of this decline was due to concerns about the toxicity and potential carcinogenicity of chronic arsenic administration. The rebirth of arsenic therapy occurred in the 1970s when physicians in China began using arsenic trioxide as part of a treatment for acute promyelocytic leukemia (APL). Their accumulated experience showed that a stable solution of arsenic trioxide given by intravenous infusion was remarkably safe and effective both in patients with newly diagnosed APL leukemia and in those with refractory and relapsed APL. The mechanisms of action of arsenic derivatives in this disease and other malignancies are many and include induction of apoptosis, partial cytodifferentiation, inhibition of proliferation, and inhibition of angiogenesis. Molecular studies and ongoing clinical trials suggest that, as a chemotherapeutic agent, arsenic trioxide shows great promise in the treatment of malignant disease.