Abstract
Lack of relevant preclinical models that reliably recapitulate the complexity and heterogeneity of human cancer has slowed down the development and approval of new anti-cancer therapies. Even though two-dimensional in vitro culture models remain widely used, they allow only partial cell-to-cell and cell-to-matrix interactions and therefore do not represent the complex nature of the tumor microenvironment. Therefore, better models reflecting intra-tumor heterogeneity need to be incorporated in the drug screening process to more reliably predict the efficacy of drug candidates. Classic methods of modelling colorectal carcinoma (CRC), while useful for many applications, carry numerous limitations. In this review, we address the recent advances in in vitro CRC model systems, ranging from conventional CRC patient-derived models, such as conditional reprogramming-based cell cultures, to more experimental and state-of-the-art models, such as cancer-on-chip platforms or liquid biopsy.
Highlights
Colorectal carcinoma (CRC) is the third most commonly diagnosed form of cancer in the world, with an estimated incidence of 1.8 million cases in 2018, and is expected to reach 2.2 million by 2030 [1,2]. cancer treatment in general has improved over the past few decades, the need for more personalized targeted therapies remains present, for late-stage metastatic CRCpatients for whom treatment options—and overall survival rates—are limited [3].The attrition rate of anticancer drugs candidates is very high, and only approximately 5% of drugs successfully complete phase III clinical trials [4,5]
The main traits of an “ideal” CRC model for testing new treatment options reside in its capacity to resemble the in vivo conditions
Different studies have demonstrated the potential use of patient-derived xenograft (PDX) as a preclinical model in the drug screening cascade, as it can reliably predict and recapitulate CRC patient drug responses in colorectal cancer [9,10,11,12,13,14,15]
Summary
Colorectal carcinoma (CRC) is the third most commonly diagnosed form of cancer in the world, with an estimated incidence of 1.8 million cases in 2018, and is expected to reach 2.2 million by 2030 [1,2]. The main traits of an “ideal” CRC model for testing new treatment options reside in its capacity to resemble the in vivo conditions. Different studies have demonstrated the potential use of PDX as a preclinical model in the drug screening cascade, as it can reliably predict and recapitulate CRC patient drug responses in colorectal cancer [9,10,11,12,13,14,15]. In PDX models the microenvironment of the subcutaneous space differs greatly from that of the colon The latter led scientists to develop orthotopic mouse models, where the tumor is directly implanted into the caecum. Current advances in tissue engineering allowed patient-derived cells to be incorporated into a bioink and bioprinted into
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