Department of Urology and Health Disparities Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nat Rev Urol. 2021 Mar;18(3):170-184. doi: 10.1038/s41585-021-00431-x. Epub 2021 Feb 26.
Therapeutic gene manipulation has been at the forefront of popular scientific discussion and basic and clinical research for decades. Basic and clinical research applications of CRISPR-Cas9-based technologies and ongoing clinical trials in this area have demonstrated the potential of genome editing to cure human disease. Evaluation of research and clinical trials in gene therapy reveals a concentration of activity in prostate cancer research and practice. Multiple aspects of prostate cancer care - including anatomical considerations that enable direct tumour injections and sampling, the availability of preclinical immune-competent models and the delineation of tumour-related antigens that might provide targets for an induced immune system - make gene therapy an appealing treatment option for this common malignancy. Vaccine-based therapies that induce an immune response and new technologies exploiting CRISPR-Cas9-assisted approaches, including chimeric antigen receptor (CAR) T cell therapies, are very promising and are currently under investigation both in the laboratory and in the clinic. Although laboratory and preclinical advances have, thus far, not led to oncologically relevant outcomes in the clinic, future studies offer great promise for gene therapy to become established in prostate cancer care.
治疗性基因操作一直是几十年来热门科学讨论和基础及临床研究的前沿。基于 CRISPR-Cas9 的技术的基础和临床研究应用以及该领域正在进行的临床试验表明,基因组编辑有可能治愈人类疾病。对基因治疗的研究和临床试验的评估显示,前列腺癌研究和实践的活动集中。前列腺癌治疗的多个方面——包括能够进行直接肿瘤注射和采样的解剖学考虑因素、临床前免疫相容模型的可用性以及可能为诱导免疫系统提供目标的肿瘤相关抗原的划定——使基因治疗成为这种常见恶性肿瘤的一种有吸引力的治疗选择。基于疫苗的治疗方法可诱导免疫反应,以及利用 CRISPR-Cas9 辅助方法的新技术,包括嵌合抗原受体 (CAR) T 细胞疗法,非常有前途,目前正在实验室和临床中进行研究。尽管实验室和临床前的进展迄今为止并未在临床上导致肿瘤学相关的结果,但未来的研究为基因治疗在前列腺癌治疗中得到确立提供了很大的希望。