Agarwal Bharat
Department of Pediatric Hematology and Oncology, B.J. Wadia Hospital for Children, Institute of Child Health and Research Centre, Mumbai, India.
Indian J Pediatr. 2008 Aug;75(8):839-44. doi: 10.1007/s12098-008-0156-9.
Biologicals are defined as agents that are either uniquely or partially tumor-specific. Great expectations were raised by the success in agents that target a specific genetic translocation: all-trans retinoic acid, targeting the chronic myeloid leukemia retinoic acid receptor in acute promyelocytic leukemia and imatinib, a small molecule targeting the BCR-ABL translocation in chronic myeloid leukemia (CML). Thus far, the search for similar "druggable" genetic targets in pediatric cancers has not yet resulted in such dramatic results. The rarity of pediatric cancer as well as ethical considerations necessitate that the agents for testing be carefully and rigorously selected. Biologicals present an additional challenge, as they often do not lend themselves to in vitro testing. Early approaches to specific targeting of solid tumors utilized monoclonal antibodies. The microenvironment provides an interesting new biological approach to treating tumors and alteration of the host immune response provides another avenue. Biological agents are a step forward in supportive care to reduce the hematological toxicity of high-dose chemotherapy and to manage the frequent infectious complications.
生物制剂被定义为具有独特或部分肿瘤特异性的药物。针对特定基因易位的药物取得成功，引发了人们的巨大期望：全反式维甲酸，它在急性早幼粒细胞白血病中靶向慢性粒细胞白血病维甲酸受体；伊马替尼，一种靶向慢性粒细胞白血病（CML）中BCR-ABL易位的小分子药物。到目前为止，在儿童癌症中寻找类似的“可成药”基因靶点尚未取得如此显著的成果。儿童癌症的罕见性以及伦理考量使得用于测试的药物必须经过仔细和严格的筛选。生物制剂带来了额外的挑战，因为它们通常不适合进行体外测试。早期针对实体瘤的特异性靶向方法使用单克隆抗体。微环境为治疗肿瘤提供了一种有趣的新生物学方法，而改变宿主免疫反应则提供了另一条途径。生物制剂在支持性治疗方面向前迈进了一步，可降低高剂量化疗的血液学毒性，并处理频繁出现的感染并发症。
