STTT：上海九院李青峰/谢峰团队揭示巨痣/兽皮病致病新机制，并提出治疗新策略

Core Viewpoint - The study presents a novel therapeutic strategy for Giant Congenital Melanocytic Nevus (GCMN) through anti-BCL2 therapy, which induces senolytic effects and immune activation to eliminate GCMN lesions [3][19]. Group 1: Disease Overview - GCMN is a benign skin condition characterized by extensive pigmentation present at birth, occurring in approximately 1 in 20,000 newborns [1]. - The condition can pose life-threatening risks, with 3%-8% of cases potentially developing into malignant melanoma and 5%-8% into neurocutaneous melanocytosis [1]. - GCMN significantly impacts patients' quality of life due to disfigurement and severe itching, increasing the likelihood of mental health issues [1]. Group 2: Current Treatment Limitations - Current treatments, including surgical excision, dermabrasion, and laser therapy, often fail to completely remove GCMN lesions, especially those larger than 60 cm, and may lead to scarring or recurrence [2]. - Existing therapies primarily target proliferation pathways but do not address the survival of GCMN cells, indicating a need for more effective drug therapies [6][9]. Group 3: Research Findings - The study identifies key somatic mutations (NRAS 68%, BRAF 7%, and RAF fusion 5%) that drive GCMN, activating MAPK and PI3K-AKT pathways [6]. - GCMN cells exhibit a dual characteristic of senescence and anti-apoptosis, with high expression of P16 and BCL2, indicating a protective mechanism against proliferation [8][9]. - The research team found that BCL2 inhibitors (BCL2i) effectively induce apoptosis in GCMN cells and prevent recurrence by targeting both senescent and proliferative cells [12][19]. Group 4: Immune Response and Long-term Effects - The study demonstrates that BCL2i not only promotes GCMN cell clearance but also triggers an immune response, recruiting neutrophils to aid in the elimination of GCMN [15][18]. - Long-term follow-up (1 year) showed no recurrence of GCMN, with residual neutrophils and T cells indicating a memory immune response [18]. Group 5: Future Directions - The findings provide a foundation for clinical trials aimed at developing targeted drug formulations for GCMN treatment, addressing the current lack of effective therapies [20].