Bu Wen, Li Yi
Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA
Cold Spring Harb Perspect Med. 2024 Mar 1;14(3):a041328. doi: 10.1101/cshperspect.a041328.
Rodent models of breast cancer have played critical roles in our understanding of breast cancer development and progression as well as preclinical testing of cancer prevention and therapeutics. In this article, we first review the values and challenges of conventional genetically engineered mouse (GEM) models and newer iterations of these models, especially those with inducible or conditional regulation of oncogenes and tumor suppressors. Then, we discuss nongermline (somatic) GEM models of breast cancer with temporospatial control, made possible by intraductal injection of viral vectors to deliver oncogenes or to manipulate the genome of mammary epithelial cells. Next, we introduce the latest development in precision editing of endogenous genes using in vivo CRISPR-Cas9 technology. We conclude with the recent development in generating somatic rat models for modeling estrogen receptor-positive breast cancer, something that has been difficult to accomplish in mice.
乳腺癌啮齿动物模型在我们对乳腺癌发生发展的理解以及癌症预防和治疗的临床前测试中发挥了关键作用。在本文中,我们首先回顾传统基因工程小鼠(GEM)模型及其更新版本的价值和挑战,特别是那些对癌基因和肿瘤抑制基因具有诱导或条件性调控的模型。然后,我们讨论通过导管内注射病毒载体来递送癌基因或操纵乳腺上皮细胞基因组从而实现时空控制的乳腺癌非种系(体细胞)GEM模型。接下来,我们介绍利用体内CRISPR-Cas9技术对内源基因进行精确编辑的最新进展。我们最后总结了生成用于模拟雌激素受体阳性乳腺癌的体细胞大鼠模型的最新进展,这在小鼠中一直难以实现。