决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
英文原题:Emerging Biomarker-Guided Therapies in Prostate Cancer.
Emerging Biomarker-Guided Therapies in Prostate Cancer.
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前列腺癌仍是全球男性癌症死亡的主要原因之一。过去十年,已有多种晚期前列腺癌新疗法获批。当前可用药物种类繁多,包括细胞毒性药物、雄激素受体轴靶向疗法及α粒子放射治疗,如何确定最佳治疗顺序仍具挑战。对前列腺癌生物学的深入理解,为更精细、个体化的治疗选择提供了机会。随着分子测序技术进步,通过识别潜在治疗靶点和预测性生物标志物实现基因组精准治疗的进展迅速。本综述讨论由生物标志物指导的晚期前列腺癌治疗。首先介绍晚期疾病既有全球标准治疗(如化疗和雄激素受体轴靶向药物)的预测性生物标志物;还讨论近期获批用于特定人群的靶向药物,包括用于同源重组修复缺陷型转移性去势抵抗性前列腺癌患者的多聚ADP核糖聚合酶(PARP)抑制剂,用于微卫星高度不稳定或肿瘤突变负荷高患者的帕博利珠单抗,以及针对PSMA表达肿瘤的前列腺特异性膜抗原(PSMA)靶向放射性配体诊疗。
此外,还讨论不断发展的疗法,如癌症疫苗、CAR-T 细胞、双特异性T细胞衔接器(BiTE)、AKT抑制剂等靶向药物及多种联合治疗。
总之,分子遗传学进展已开始推动晚期前列腺癌个体化医疗,使基于生物标志物、更精准的治疗选择成为可能,目标是提升总体疗效。
Prostate cancer remains one of the leading causes of cancer death in men worldwide. In the past decade, several new treatments for advanced prostate cancer have been approved. With a wide variety of available drugs, including cytotoxic agents, androgen receptor axis-targeted therapies, and alpha-emitting radiation therapy, identifying their optimal sequencing remains a challenge. Progress in the understanding of the biology of prostate cancer has provided an opportunity for a more refined and personalized treatment selection process.
With the advancement of molecular sequencing techniques, genomic precision through the identification of potential treatment targets and predictive biomarkers has been rapidly evolving. In this review, we discussed biomarker-driven treatments for advanced prostate cancer. First, we presented predictive biomarkers for established, global standard treatments for advanced diseases, such as chemotherapy and androgen receptor axis-targeted agents.
We also discussed targeted agents with recent approval for special populations, such as poly ADP ribose polymerase (PARP) inhibitors in patients with metastatic castrate-resistant prostate cancer with homologous recombination repair-deficient tumors, pembrolizumab in patients with high levels of microsatellite instability or high tumor mutational burden, and prostate-specific membrane antigen (PSMA) directed radioligand theragnostic treatment for PSMA expressing tumors.
Additionally, we discussed evolving treatments, such as cancer vaccines, chimeric antigen receptor T-cells (CAR-T), Bispecific T-cell engagers (BiTEs), other targeted agents such as AKT inhibitors, and various combination treatments. In summary, advances in molecular genetics have begun to propel personalized medicine forward in the management of advanced prostate cancer, allowing for a more precise, biomarker-driven treatment selection with the goal of improving overall efficacy.
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