IIGM - Italian Institute for Genomic Medicine, c/o IRCSS Candiolo, Torino, Italy.
Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Italy.
Nat Med. 2021 Feb;27(2):212-224. doi: 10.1038/s41591-021-01233-9. Epub 2021 Feb 11.
Most (if not all) tumors emerge and progress under a strong evolutionary pressure imposed by trophic, metabolic, immunological, and therapeutic factors. The relative impact of these factors on tumor evolution changes over space and time, ultimately favoring the establishment of a neoplastic microenvironment that exhibits considerable genetic, phenotypic, and behavioral heterogeneity in all its components. Here, we discuss the main sources of intratumoral heterogeneity and its impact on the natural history of the disease, including sensitivity to treatment, as we delineate potential strategies to target such a detrimental feature of aggressive malignancies.
大多数（如果不是全部）肿瘤都是在营养、代谢、免疫和治疗等因素施加的强大进化压力下出现和发展的。这些因素对肿瘤进化的相对影响随着空间和时间的变化而变化，最终有利于建立一个肿瘤微环境，使其所有成分都表现出相当大的遗传、表型和行为异质性。在这里，我们讨论了肿瘤内异质性的主要来源及其对疾病自然史的影响，包括对治疗的敏感性，同时我们还描绘了针对这种侵袭性恶性肿瘤的有害特征的潜在策略。
