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免疫治疗和小分子癌症治疗对生育力的影响:当前证据、机制和未来方向的叙述性综述

英文原题:Impact of immunotherapy and small molecule cancer therapy on fertility: a narrative review of current evidence, mechanisms and future directions.

PubMed 2026/01/28(内容时间) BMJ Oncol

研究概要

随着育龄人群癌症发病率的增加,保留生育能力已成为癌症治疗中的一个关键方面。

中文摘要

随着育龄人群癌症发病率的增加,保留生育能力已成为癌症治疗中的一个关键方面。本叙述性综述探讨了当代癌症治疗(包括免疫治疗和靶向药物)对生殖健康的影响,重点介绍了临床生育结局及其潜在的生物学机制。我们概述了青少年和年轻成人(AYAs)中常见恶性肿瘤的流行病学和治疗策略,包括乳腺癌、黑色素瘤、肺癌、妇科癌症、结直肠癌和血液系统恶性肿瘤。综述了男性和女性的基本生殖生理学,包括下丘脑-垂体-性腺轴、卵巢卵泡和卵母细胞发育以及精子发生。总结了接受免疫治疗或靶向治疗患者的生育和生殖结局相关临床数据,以及传统化疗和新型药物类别的性腺毒性推测机制。特别强调了免疫治疗,如检查点抑制剂、细胞疗法(例如CAR-T 细胞、TIL(肿瘤浸润淋巴细胞)和单克隆抗体,以及小分子抑制剂,包括激酶抑制剂(例如BRAF、MEK、表皮生长因子受体)、聚(ADP-核糖)聚合酶抑制剂、表观遗传修饰剂和凋亡促进剂(例如BCL-2抑制剂)。尽管这些疗法的使用日益增多,但其在生殖安全性方面的研究仍不充分,现有证据有限、异质性大,且往往缺乏基线生育评估或长期随访。这种不确定性使咨询和决策变得复杂,需要对生育力保存采取预防性措施。多学科协作,整合肿瘤学、生殖医学、心理学和伦理学,对于个体化、伦理合理的照护至关重要。器官芯片系统和诱导多能干细胞模型等新兴技术为机制洞察提供了有前景的途径。为推动该领域发展,未来工作必须聚焦于前瞻性队列研究、稳健的临床前模型和 interim 临床指南,以支持癌症患者获得知情的生育相关照护。

展开英文摘要原文

With increasing cancer incidence among individuals of reproductive age, preserving fertility has become a critical aspect of cancer care. This narrative review explores the impact of contemporary cancer therapies, including immunotherapies and targeted agents, on reproductive health, highlighting clinical fertility outcomes and underlying biological mechanisms. We outline the epidemiology and treatment strategies for malignancies common in adolescents and young adults (AYAs), including breast, melanoma, lung, gynaecologic, colorectal cancers and haematologic malignancies. Basic reproductive physiology in males and females is reviewed, including the hypothalamic-pituitary-gonadal axis, ovarian follicle and oocyte development, and spermatogenesis. Clinical data related to fertility and reproductive outcomes in patients receiving immunotherapy or targeted therapy are summarised, along with proposed mechanisms of gonadotoxicity from both conventional chemotherapy and newer drug classes. Special emphasis is placed on immunotherapy, such as checkpoint inhibitors, cell-based therapies (eg, chimeric antigen receptor T cells, tumour-infiltrating lymphocytes) and monoclonal antibodies, and small-molecule inhibitors, including kinase inhibitors (eg, BRAF, MEK, epidermal growth factor receptor), poly (ADP-ribose) polymerase inhibitors, epigenetic modifiers and apoptosis promoters (eg, BCL-2 inhibitors). Despite their growing use, these therapies are poorly studied in terms of reproductive safety, with available evidence being limited, heterogeneous and often lacking baseline fertility assessments or long-term follow-up. This uncertainty complicates counselling and decision-making, requiring a precautionary approach to fertility preservation. Multidisciplinary collaboration incorporating oncology, reproductive medicine, psychology and ethics is essential for individualised, ethically sound care. Emerging technologies such as organ-on-chip systems and induced pluripotent stem cell models offer promising avenues for mechanistic insight. To advance the field, future efforts must focus on prospective cohort studies, robust preclinical models and interim clinical guidelines to support informed fertility-related care for cancer patients.

论文信息

作者
Gargus E、Kuribayashi S、Lundy SD、Rotz S、Alkhouli L、Bussies PL、Falcone T
单位
Obstetrics & Gynecology, Cleveland Clinic, Cleveland, Ohio, USA.United States
文献类型
综述
期刊
BMJ oncology2026
原文标识
PubMed 41623933 · DOI 10.1136/bmjonc-2025-000843