Patient-derived rectal cancer organoids-applications in basic and translational cancer research

Abstract

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and among the leading causes of death in both men and women. Rectal cancer (RC) is particularly challenging compared with colon cancer as the treatment after diagnosis of RC is more complex on account of its narrow anatomical location in the pelvis adjacent to the urogenital organs. More and more existing studies have begun to refine the research on RC and colon cancer separately. Early diagnosis and multiple treatment strategies optimize outcomes for individual patients. However, the need for more accurate and precise models to facilitate RC research is underscored due to the heterogeneity of clinical response and morbidity interrelated with radical surgery. Organoids generated from biopsies of patients have developed as powerful models to recapitulate many aspects of their primary tissue, consisting of 3-D self-organizing structures, which shed great light on the applications in both biomedical and clinical research. As the preclinical research models for RC are usually confused with colon cancer, research on patient-derived RC organoid models enable personalized analysis of cancer pathobiology, organizational function, and tumor initiation and progression. In this review, we discuss the various applications of patient-derived RC organoids over the past two years in basic cancer biology and clinical translation, including sequencing analysis, drug screening, precision therapy practice, tumor microenvironment studies, and genetic engineering opportunities.

Keywords: cancer modeling; organoids; patient-derived; precision medicine; rectal cancer; treatment prediction; tumor microenvironment.

Figure 1

Developments and cutting-edge applications of the PDO model. (A) After an RC patient tumor’s surgery or biopsy, the tumor specimen is collected. PDOs can be generated in the laboratory and expanded to create sufficient material for biobank building and storage. Once established, these models are expanded in order to create sufficient material for storage and biobanking. (B) Multiple applications in vitro or ex vivo can be performed, such as genome profiling, drug screening, coculture experiments, etc.