5-FU resistance mechanisms in colorectal cancer: from classical pathways to promising processes

Colorectal Cancer

Blondy S, et al. Cancer Sci 2020 - Review.


Colorectal cancer (CRC) is a public health problem. It is the third most common cancer in the world, with nearly 1.8 million new cases diagnosed in 2018. The only curative treatment is surgery, especially for early tumor stages. When there is locoregional or distant invasion, chemotherapy can be introduced, in particular 5 Fluorouracil (5-FU). However, the disease can become tolerant to these pharmaceutical treatments: resistance emerged, leading to early tumor recurrence. Different mechanisms

can explain these 5-FU-resistances. Some are disease-specific, while others, such as drug efflux, are evolutionarily conserved. These mechanisms are numerous and complex and can occur simultaneously in cells exposed to 5-FU. In this review, we make a global outline of different mechanisms from disruption of 5-FU-metabolic enzymes, classic cellular processes (apoptosis, autophagy, glucose metabolism, oxidative stress, respiration and cell cycle perturbation), as well as drug-transporters and epithelial-mesenchymal transition (EMT) induction. In the end, a particular interest is dressed on Tumor Microenvironment (TME) function and also on epigenetic alterations and miRNA dysregulation, which are the more promising processes that will be the subject of much research in the future.