RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
肿瘤细胞治疗研究
英文原题:Pediatric Melanoma: Emerging Therapies and Ongoing Clinical Trials.
Pediatric Melanoma: Emerging Therapies and Ongoing Clinical Trials.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
儿童黑色素瘤较为罕见,且具有独特的临床特征,占所有黑色素瘤病例的1%–4%。其亚型包括Spitz样黑色素瘤、先天性色素痣相关黑色素瘤及常规型黑色素瘤,各自具有特定的生物学行为和治疗意义。手术切除仍是主要治疗方式;全身治疗通常借鉴成人方案并超说明书使用,而儿童特异性的疗效、剂量和安全性数据有限。本叙述性综述总结当前治疗方法,包括免疫检查点抑制剂和靶向治疗的应用,并介绍现有前瞻性及回顾性研究结局。此外,综述还回顾了探索新策略的在研临床试验,如嵌合抗原受体(CAR)T细胞疗法、自然杀伤(NK)细胞输注、Wnt/β-catenin通路抑制剂及癌症疫苗。尽管关注度不断上升,疾病罕见、长期毒性数据缺乏及基于生物标志物的分层有限,仍构成挑战。扩大儿童专属临床研究、整合分子谱分析,并关注发育和心理社会需求,对于改善诊疗至关重要。在研试验有望推动开发更安全、更有效且适合这一脆弱人群的治疗方案。
Pediatric melanoma is a rare but clinically distinct malignancy, accounting for 1-4% of all melanoma cases. It encompasses unique subtypes-Spitzoid melanoma, melanoma arising in congenital melanocytic nevi, and conventional melanoma-each with specific biological behavior and therapeutic implications.
While surgical excision remains the primary treatment, systemic therapies are often adapted from adult protocols and used off-label, with limited pediatric-specific data on efficacy, dosing, and safety. This narrative review summarizes current treatment approaches, including the use of immune checkpoint inhibitors and targeted therapies, and highlights outcomes from available prospective and retrospective studies.
Furthermore, it reviews ongoing clinical trials investigating novel strategies such as chimeric antigen receptor (CAR) T-cell therapy, natural killer (NK) cell infusions, Wnt/ -catenin pathway inhibitors, and cancer vaccines. Despite emerging interest, challenges persist due to the rarity of the disease, lack of long-term toxicity data, and limited biomarker-driven stratification.
Expanding pediatric-focused clinical research, integrating molecular profiling, and addressing developmental and psychosocial needs are essential for advancing care. Ongoing trials may help pave the way for safer and more effective therapies tailored to this vulnerable population.
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