Gutmann David H, Boehm Jesse S, Karlsson Elinor K, Padron Eric, Seshadri Mukund, Wallis Deeann, Snyder Joshua C
Department of Neurology, Washington University, St Louis, MO 63110, United States.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, United States.
J Natl Cancer Inst. 2025 Apr 1;117(4):586-594. doi: 10.1093/jnci/djae249.
A new era of cancer management is underway in which treatments are being developed for the entire continuum of the disease process. The availability of genetically engineered and naturally occurring preclinical models serves as instructive platforms for evaluating therapeutic mechanisms. However, a major clinical challenge is that the entire malignancy process occurs across multiple scales including genetic mutations, malignant changes in cell behavior, dysregulated tumor microenvironments, and systemic adaptations in the host. A multidisciplinary group of investigators coalesced at the National Cancer Institute Oncology Models Forum with the overall goal to provide updates on the use of precision preclinical models of cancer. The benefits and limitations of preclinical models were discussed to identify strategies for maximizing opportunities in modeling that could inform future cancer prevention and treatment approaches. Our shared perspective is that the continuum of single cell, multicell, organoid, and in situ models are remarkable resources for the clinical challenges ahead. We provide a roadmap for parsing already available models and include preliminary recommendations for the application of next-generation preclinical modeling in cancer intervention.
癌症治疗的新时代正在开启，针对疾病全过程的治疗方法正在研发中。基因工程改造的和天然存在的临床前模型为评估治疗机制提供了具有指导意义的平台。然而，一个主要的临床挑战是，整个恶性肿瘤过程发生在多个尺度上，包括基因突变、细胞行为的恶性变化、失调的肿瘤微环境以及宿主的全身适应性。一组多学科研究人员齐聚美国国立癌症研究所肿瘤模型论坛，总体目标是提供癌症精准临床前模型使用情况的最新信息。讨论了临床前模型的优点和局限性，以确定在建模中最大化机会的策略，这些策略可为未来的癌症预防和治疗方法提供参考。我们共同的观点是，单细胞、多细胞、类器官和原位模型的连续体是应对未来临床挑战的宝贵资源。我们提供了一个解析现有模型的路线图，并包括关于下一代临床前建模在癌症干预中应用的初步建议。
