UNASSIGNED: Current pharmacological advancements in CML therapy focus on targeting LSCs, intervening in self-renewal pathways, and exploiting biological vulnerabilities. Beyond BCR::ABL1 inhibition, innovative approaches include immunotherapy, epigenetic modulation, and interference with microenvironmental mechanisms.
UNASSIGNED: Diverse therapeutic strategies beyond TKIs are under investigation. Immunotherapy with interferon-α (IFN-α) shows some biological effects, although further research is needed for optimal application in enhancing discontinuation rates. Other compounds were able to mobilize Ph+ LSCs from the bone marrow niche (DPP-IV inhibitor vildagliptin or PAI-1 inhibitor TM5614) increasing the LSC clearance or target the CD26, a Ph+ specific surface receptor. It is noteworthy that the majority of these alternative strategies still incorporate TKIs. In conclusion, novel therapeutic perspectives are emerging for CML, holding the potential for substantial advancements in disease treatment.
■当前CML治疗的药理学进展集中于靶向LSCs,干预自我更新途径,利用生物脆弱性。超过BCR::ABL1抑制,创新的方法包括免疫疗法,表观遗传调制,和干扰微环境机制。
■除TKIs之外的多种治疗策略正在研究中。干扰素-α(IFN-α)的免疫治疗显示出一定的生物学效应,尽管在提高停药率方面的最佳应用还需要进一步研究。其他化合物能够从骨髓生态位(DPP-IV抑制剂维格列汀或PAI-1抑制剂TM5614)动员Ph+LSC,增加LSC清除率或靶向CD26,Ph+特异性表面受体。值得注意的是,这些替代策略中的大多数仍然包含TKIs。总之,CML出现了新的治疗观点,保持疾病治疗取得实质性进展的潜力。