Re-thinking therapeutic development for CNS metastatic disease.
Re-thinking therapeutic development for CNS metastatic disease.
复制标题
重新思考中枢神经系统转移性疾病的治疗开发。
DOI：
10.1111/exd.14413
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发表时间：
2022
影响因子：
3.6
通讯作者：
Davies,MichaelA
中科院分区：
文献类型：
--
作者：
Saberian,Chantal;Davies,MichaelA
在过去的十年里，对于转移性黑色素瘤患者的系统治疗的发展取得了前所未有的进步。现在有巨大的潜力和势头来进一步和显著地减少这一疾病的影响。然而，对于黑色素瘤患者来说，开发更有效的转移到中枢神经系统的治疗方法仍然是一个关键的挑战。有活跃的中枢神经系统转移的黑色素瘤患者在很大程度上被排除在目前批准的所有针对这种疾病的靶向和免疫疗法的早期阶段和注册试验之外。尽管由于担心预后不良、药物缺乏中枢神经系统渗透和/或毒性风险，这种排除在临床研究中通常是合理的，但最近批准后的试验表明，在这些患者中进行临床研究是可行的、安全的和临床上的好处。这些试验还确定了需要更有效战略的关键领域。与此同时，最近的翻译和临床前研究提供了对黑色素瘤脑转移的新的免疫、分子和代谢特征的见解，这些特征可能介导这些肿瘤的侵袭性生物学和治疗耐药性。综上所述，这些进展表明有必要为中枢神经系统转移的黑色素瘤患者的治疗开发提供新的范例。
There has been unprecedented progress in the development of systemic therapies for patients with metastatic melanoma over the last decade. There is now tremendous potential and momentum to further and markedly reduce the impact of this disease. However, developing more effective treatments for metastases to the CNS remains a critical challenge for patients with melanoma. Melanoma patients with active CNS metastases have largely been excluded from both early‐phase and registration trials for all currently approved targeted and immune therapies for this disease. While this exclusion has generally been justified in clinical research due to concerns about poor prognosis, lack of CNS penetration of agents and/or risk of toxicities, recent post‐approval trials have shown the feasibility, safety and clinical benefit of clinical investigation in these patients. These trials have also identified key areas for which more effective strategies are needed. In parallel, recent translational and preclinical research has provided insights into novel immune, molecular and metabolic features of melanoma brain metastases that may mediate the aggressive biology and therapeutic resistance of these tumors. Together, these advances suggest the need for new paradigms for therapeutic development for melanoma patients with CNS metastasis.