Lodhia K A, Hadley A M, Haluska P, Scott C L
Department of Oncology, Mayo Clinic, Rochester, MN, USA.
Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Biochim Biophys Acta. 2015 Apr;1855(2):223-34. doi: 10.1016/j.bbcan.2015.03.002. Epub 2015 Mar 14.
Effective systemic treatment of cancer relies on the delivery of agents with optimal therapeutic potential. The molecular age of medicine has provided genomic tools that can identify a large number of potential therapeutic targets in individual patients, heralding the promise of personalized treatment. However, determining which potential targets actually drive tumor growth and should be prioritized for therapy is challenging. Indeed, reliable molecular matches of target and therapeutic agent have been stringently validated in the clinic for only a small number of targets. Patient-derived xenografts (PDXs) are tumor models developed in immunocompromised mice using tumor procured directly from the patient. As patient surrogates, PDX models represent a powerful tool for addressing individualized therapy. Challenges include humanizing the immune system of PDX models and ensuring high quality molecular annotation, in order to maximize insights for the clinic. Importantly, PDX can be sampled repeatedly and in parallel, to reveal clonal evolution, which may predict mechanisms of drug resistance and inform therapeutic strategy design.
癌症的有效全身治疗依赖于递送具有最佳治疗潜力的药物。医学的分子时代提供了基因组工具，这些工具可以识别个体患者中的大量潜在治疗靶点，预示着个性化治疗的前景。然而，确定哪些潜在靶点实际上驱动肿瘤生长并应优先用于治疗具有挑战性。事实上，靶标与治疗药物之间可靠的分子匹配仅在临床上针对少数靶标进行了严格验证。患者来源的异种移植瘤（PDX）是在免疫缺陷小鼠中使用直接从患者获取的肿瘤建立的肿瘤模型。作为患者替身，PDX模型是解决个体化治疗的有力工具。挑战包括使PDX模型的免疫系统人源化并确保高质量的分子注释，以便最大限度地为临床提供见解。重要的是，PDX可以重复且并行采样，以揭示克隆进化，这可能预测耐药机制并为治疗策略设计提供依据。
