Cancer Therapies and Biology Group, Centre for Research Excellence in Brain Cancer, Olivia Newton-John Cancer Research Institute, Austin Health, 145 Studley Road, Heidelberg, Melbourne, VIC, 3084, Australia.
La Trobe University School of Cancer Medicine, Heidelberg, VIC, Australia.
Curr Oncol Rep. 2023 Jun;25(6):589-598. doi: 10.1007/s11912-023-01394-5. Epub 2023 Mar 28.
This review identifies challenges and barriers to successful development of drugs in neuro-oncology trials at the preclinical, clinical and translational stages that we believe has contributed to poor outcomes for patients over the last 30 years.
Several key strategies have been proposed by leading groups to address these and improve patient outcomes. Better preclinical testing using more sophisticated and clinically relevant models is needed. A greater focus on assessing blood-brain barrier penetrance and targeting key biological processes such as tumour heterogeneity and immune response is vital. Adopting innovative trial designs permitting faster results and addressing key issues (including molecular heterogeneity and combinatorial approaches) is highly desirable. A stronger translational focus is also clearly needed. Implementation of these strategies is already starting to occur. Maintaining and increasing these novel approaches will require coordinated efforts between clinicians, scientists, industry and funding/regulator bodies.
本综述确定了神经肿瘤学试验在临床前、临床和转化阶段药物开发成功所面临的挑战和障碍，我们认为这导致了过去 30 年来患者的治疗效果不佳。
一些主要的研究团队提出了一些关键的策略来解决这些问题，改善患者的预后。需要使用更复杂和更具临床相关性的模型进行更好的临床前测试。更注重评估血脑屏障穿透性以及针对肿瘤异质性和免疫反应等关键生物学过程至关重要。采用允许更快获得结果并解决关键问题（包括分子异质性和组合方法）的创新试验设计是非常可取的。还需要明确加强转化研究的重点。这些策略的实施已经开始。保持和增加这些新方法需要临床医生、科学家、工业界以及资金/监管机构之间的协调努力。
