Memorial Sloan Kettering Cancer Center, New York, NY.
Adv Anat Pathol. 2024 Mar 1;31(2):70-79. doi: 10.1097/PAP.0000000000000431. Epub 2024 Jan 15.
Treatment-related neuroendocrine prostate cancer is a distinctive category of prostate cancer that arises after intensive suppression of the androgen receptor by next-generation therapeutic inhibition of androgen receptor signaling. The biological processes that set in motion the series of events resulting in transformation of adenocarcinoma to neuroendocrine carcinoma include genomic (loss of tumor suppressors TP53 and RB1, amplification of oncogenes N-MYC and Aurora Kinase A, dysregulation of transcription factors SOX2, achaete-scute-homolog 1, and others) as well as epigenomic (DNA methylation, EZH2 overexpression, and others). Pathologic diagnosis is key to effective therapy for this disease, and this is aided by localizing metastatic lesions for biopsy using radioligand imaging in the appropriate clinical context. As our understanding of biology evolves, there has been increased morphologic recognition and characterization of tumor phenotypes that are present in this advanced post-treatment setting. New and promising biomarkers (delta-like ligand 3 and others) have been discovered, which opens up novel therapeutic avenues including immunotherapy and antibody-drug conjugates for this lethal disease with currently limited treatment options.
治疗相关的神经内分泌前列腺癌是一种独特的前列腺癌类别，它发生在下一代雄激素受体信号抑制治疗强烈抑制雄激素受体之后。引发一系列事件导致腺癌向神经内分泌癌转化的生物学过程包括基因组（肿瘤抑制基因 TP53 和 RB1 的缺失、癌基因 N-MYC 和 Aurora Kinase A 的扩增、转录因子 SOX2、achaete-scute-homolog 1 等的失调）和表观基因组（DNA 甲基化、EZH2 过表达等）。病理诊断是治疗这种疾病的关键，放射性配体成像在适当的临床环境下定位转移性病变进行活检有助于诊断。随着我们对生物学的理解不断发展，在这种先进的治疗后环境中，已经越来越多地认识和描述存在的肿瘤表型。已经发现了新的有前途的生物标志物（Delta-like ligand 3 等），这为这种目前治疗选择有限的致命疾病开辟了新的治疗途径，包括免疫疗法和抗体药物偶联物。
