Rhinehart Dena P, Lai Jiaying, Sanin David E, Vakkala Varsha, Mendes Adrianna, Bailey Christopher, Antonarakis Emmanuel S, Paller Channing J, Wu Xiaojun, Lotan Tamara L, Karchin Rachel, Sena Laura A
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Institute for Computational Medicine at Johns Hopkins University, Baltimore, MD, USA.
NPJ Precis Oncol. 2024 Dec 2;8(1):275. doi: 10.1038/s41698-024-00773-w.
Metastatic prostate cancer (PCa) is not curable due to its ability to acquire therapy resistance. Theoretically, acquired therapy resistance can be driven by changes to previously sensitive cancer cells or their environment and/or by outgrowth of a subpopulation of cancer cells with primary resistance. Direct demonstration of the latter mechanism in patients with PCa is lacking. Here we present a case report as proof-of-principle that outgrowth of a subpopulation of cancer cells lacking the genomic target and present prior to therapy initiation can drive acquired resistance to targeted therapy and threaten survival in patients with PCa.
转移性前列腺癌（PCa）因其获得性治疗耐药能力而无法治愈。理论上，获得性治疗耐药可能是由先前敏感的癌细胞或其环境的变化和/或具有原发性耐药的癌细胞亚群的增殖所驱动。在前列腺癌患者中缺乏对后一种机制的直接证明。在此，我们报告一例病例作为原理证明，即缺乏基因组靶点且在治疗开始前就已存在的癌细胞亚群的增殖可导致对靶向治疗的获得性耐药，并威胁前列腺癌患者的生存。
