Beere H M, Hickman J A
CRC Molecular and Cellular Pharmacology Group, School of Biological Sciences, University of Manchester, UK.
Anticancer Drug Des. 1993 Aug;8(4):299-322.
Differentiation therapy focuses on the development and use of specific agents designed to selectively engage the process of terminal differentiation, leading to the eventual elimination of tumorigenic cells and rebalance of normal cellular homeostasis. Extensive in vitro study of the molecular mechanism involved during drug-induced maturation has allowed the realization and application of a differentiation-based therapy to the clinic. Rationalization of this mode of therapy has included the combined use of differentiation agents with low-dose chemotherapy to lessen adverse cytotoxicity and to enhance the efficacy of differentiation agents, allowing some success in their application to conditions resistant to conventional therapy. This review discusses some biological principles that underlie the concept of a differentiation therapy and compares the in vitro and in vivo effectiveness of the two differentiation agents, in particular retinoic acid (RA) and hexamethylene bisacetamide (HMBA). It also evaluates the prospects for differentiation therapy as an effective strategy in the treatment and management of malignancy.
分化疗法专注于开发和使用特定药物，这些药物旨在选择性地参与终末分化过程，最终导致致瘤细胞的消除以及正常细胞稳态的重新平衡。对药物诱导成熟过程中涉及的分子机制进行的广泛体外研究，使得基于分化的疗法得以在临床上实现和应用。这种治疗模式的合理化包括将分化剂与低剂量化疗联合使用，以减轻不良细胞毒性并提高分化剂的疗效，从而在将其应用于对传统疗法耐药的病症方面取得了一些成功。本综述讨论了分化疗法概念背后的一些生物学原理，并比较了两种分化剂，特别是维甲酸（RA）和六甲撑双乙酰胺（HMBA）的体外和体内有效性。它还评估了分化疗法作为恶性肿瘤治疗和管理有效策略的前景。
