Department of Medical Oncology, St Bartholomew's Hospital, London, UK.
Department of Medical Oncology, University College London Hospital, London, UK.
Histopathology. 2020 Jan;76(1):157-170. doi: 10.1111/his.14009.
The treatment of cancer has changed dramatically over the last decade, driven by increased understanding of the cancer genome, immune landscape, molecular alterations and aberrant pathways that drive cancer progression. Advances in molecular biology have led to the development of targeted agents, including monoclonal antibodies, small molecules and check-point inhibitors. Unlike chemotherapy, which inhibits DNA replication and mitosis, these agents target cancer signalling pathways, stroma, immune microenvironment and vasculature in tumour tissues. In gynaecological cancer, drugs targeting defective DNA repair, such as PARP inhibitors, have been approved for advanced ovarian cancer, and drugs targeting angiogenesis have been used in the treatment of advanced or recurrent ovarian and cervical cancers. Immune check-point inhibitors such as anti-PD-1/PD-L1 antibodies have proved successful for mismatch repair-deficient endometrial cancers and HPV-targeted therapies are under development for HPV-related malignancies. In this era of precision medicine, improved understanding of cancer biology and genomics needs to be utilised to develop predictive biomarkers for these targeted therapies to maximise patient benefit.
在过去的十年中,由于对癌症基因组、免疫景观、驱动癌症进展的分子改变和异常途径的理解不断加深,癌症的治疗发生了巨大变化。分子生物学的进步导致了靶向药物的发展,包括单克隆抗体、小分子和检查点抑制剂。与抑制 DNA 复制和有丝分裂的化疗不同,这些药物针对癌症信号通路、基质、肿瘤组织中的免疫微环境和血管。在妇科癌症中,针对缺陷 DNA 修复的药物,如 PARP 抑制剂,已被批准用于晚期卵巢癌,针对血管生成的药物已用于治疗晚期或复发性卵巢和宫颈癌。免疫检查点抑制剂,如抗 PD-1/PD-L1 抗体,已被证明对错配修复缺陷型子宫内膜癌有效,针对 HPV 的靶向治疗正在开发中,用于 HPV 相关恶性肿瘤。在精准医学时代,需要利用对癌症生物学和基因组学的深入了解,为这些靶向治疗开发预测性生物标志物,以最大限度地提高患者受益。