Department of Investigational Cancer Therapeutics (Phase I Program), University of Texas, MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.
Nat Rev Clin Oncol. 2012 Nov;9(11):631-42. doi: 10.1038/nrclinonc.2012.160. Epub 2012 Sep 11.
Designation of a rare 'orphan' disease is usually conferred by a prevalence of one in 1,500 to 2,500 individuals. Increasingly, orphan diseases are also being defined by their molecular fingerprints. Rare diseases are uniquely challenging from a therapeutic standpoint; it is critical to modify clinical study design of treatments for orphan disorders as well as for the increasingly smaller molecular subsets within frequently occurring cancers. In spite of the immense challenges associated with developing a treatment for a rare disorder, some of the most groundbreaking therapeutic discoveries have been made in orphan malignancies. This situation may be because a limited number of driver molecular aberrations occur in rare disorders, which can be targeted by agents. Here, we describe drug-class examples of targeted therapies for orphan diseases, with particular emphasis on malignancies or tumour-prone nonmalignant conditions, as well as potential therapeutic strategies that can be adopted to treat these orphan conditions.
罕见“孤儿病”的定义通常是指每 1500 至 2500 个人中就有 1 人患病。越来越多的孤儿病也因其分子特征而被定义。从治疗的角度来看，罕见疾病极具挑战性；对于孤儿疾病以及在常见癌症中越来越小的分子亚群，修改治疗的临床研究设计至关重要。尽管开发罕见疾病的治疗方法面临巨大挑战，但一些最具开创性的治疗发现是在孤儿恶性肿瘤中取得的。这种情况可能是因为罕见疾病中发生的驱动分子异常数量有限，这些异常可以被药物靶向。在这里，我们描述了孤儿疾病的靶向治疗药物类别示例，特别强调了恶性肿瘤或易发生肿瘤的非恶性疾病，以及可以用来治疗这些孤儿疾病的潜在治疗策略。
