Departments of Pharmacology and Medicine, San Diego School of Medicine, University of California, La Jolla, CA, USA.
Sanford Consortium for Regenerative Medicine, San Diego School of Medicine, University of California, La Jolla, CA, USA.
Nat Rev Cancer. 2018 Nov;18(11):669-680. doi: 10.1038/s41568-018-0056-x.
Although we have come a long way in our understanding of the signals that drive cancer growth, and how these signals can be targeted, effective control of this disease remains a key scientific and medical challenge. The therapy resistance and relapse that are commonly seen are driven in large part by the inherent heterogeneity within cancers that allows drugs to effectively eliminate some, but not all, malignant cells. Here, we focus on the fundamental drivers of this heterogeneity by examining emerging evidence that shows that these traits are often controlled by the disruption of normal cell fate and aberrant adoption of stem cell signals. We discuss how undifferentiated cells are preferentially primed for transformation and often serve as the cell of origin for cancers. We also consider evidence showing that activation of stem cell programmes in cancers can lead to progression, therapy resistance and metastatic growth and that targeting these attributes may enable better control over a difficult disease.
尽管我们在理解驱动癌症生长的信号以及如何靶向这些信号方面已经取得了很大进展，但有效控制这种疾病仍然是一个关键的科学和医学挑战。治疗耐药性和复发在很大程度上是由癌症内在的异质性驱动的，这种异质性使得药物能够有效消除一些，但不是所有的恶性细胞。在这里，我们通过检查新兴的证据来关注这种异质性的基本驱动因素，这些证据表明，这些特征通常是由正常细胞命运的破坏和异常的干细胞信号的采用控制的。我们讨论了未分化细胞如何被优先诱导转化，并且经常作为癌症的起源细胞。我们还考虑了一些证据，这些证据表明癌症中干细胞程序的激活会导致进展、治疗耐药性和转移性生长，而靶向这些特征可能会更好地控制这种棘手的疾病。
