Recent Advancement in Breast Cancer Research: Insights from Model Organisms-Mouse Models to Zebrafish

Abstract

Animal models have been utilized for decades to investigate the causes of human diseases and provide platforms for testing novel therapies. Indeed, breakthrough advances in genetically engineered mouse (GEM) models and xenograft transplantation technologies have dramatically benefited in elucidating the mechanisms underlying the pathogenesis of multiple diseases, including cancer. The currently available GEM models have been employed to assess specific genetic changes that underlay many features of carcinogenesis, including variations in tumor cell proliferation, apoptosis, invasion, metastasis, angiogenesis, and drug resistance. In addition, mice models render it easier to locate tumor biomarkers for the recognition, prognosis, and surveillance of cancer progression and recurrence. Furthermore, the patient-derived xenograft (PDX) model, which involves the direct surgical transfer of fresh human tumor samples to immunodeficient mice, has contributed significantly to advancing the field of drug discovery and therapeutics. Here, we provide a synopsis of mouse and zebrafish models used in cancer research as well as an interdisciplinary 'Team Medicine' approach that has not only accelerated our understanding of varied aspects of carcinogenesis but has also been instrumental in developing novel therapeutic strategies.

Keywords: CDX models; GEM models; PDX models; drug screening; mouse; orthotopic models; zebrafish.

Figure 1

Schematic representation showing the generation of various mouse tumor models for cancer therapeutics.

Figure 2

An overall schematic representation of patient-derived xenograft (PDX) generation. (A) Fragmentation of tumor tissue, followed by subcutaneous or orthotopic implantation, (B) Processing of tumor tissue as a single cell suspension, followed by subsequent implantation.

Figure 3

Generation and application of zebrafish models in cancer research. The tumor tissue obtained from patients is sectioned and processed and is transplanted into zebrafish larvae 48 h post-fertilization to create zPDXs. zPDX provides an effective platform for screening potential cancer drug candidates and evaluating cancer cell growth. Another major application of zebrafish is the generation of transgenic. The mutated DNA is microinjected into the zebrafish embryos for knockdown or overexpression of the disease target gene, followed by phenotypic observation.