Tumor Environment Modulation and Modeling through Exosomal Delivery of microRNAs in Colorectal Cancer Organoids

Abstract

Internal and external aspects of the tumor microenvironments have impaired the treatment of colorectal cancer (CRC). Characteristics of these environments facilitate continued tumor survival and resistance to treatment. This includes expression of factors which facilitate continued tumor growth in a hypoxic environment as well as immunosuppression. Therefore, in order to adequately treat CRC, both the internal and external aspects of the tumor microenvironment must be addressed. Furthermore, inadequate delivery methods and modeling of the patient specific tumor impedes treatment. A proposed method to target these characteristics of CRC involves microRNA delivery via exosomes. MicroRNAs targeting protein expression that enable aspects of the internal and external tumor microenvironment delivered by exosomes will reduce tumor growth. Exosomes delivered to patient-derived organoids will enable specific delivery of microRNAs to the tumor site and modeling of patient specific immune interactions. A review of current literature suggests that a combination of these methods will be effective to treat CRC. In this review miR-34a and miR-138-5p have been indicated to inhibit the expression of the Wnt/β-Catenin and PD-L1 pathways respectively.