Epigenetics and chemoresistance in colorectal cancer: An opportunity for treatment tailoring and novel therapeutic strategies |
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| Authors: | Francesco Crea Stefania Nobili Elisa Paolicchi Gabriele Perrone Cristina Napoli Ida Landini Romano Danesi Enrico Mini |
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| Affiliation: | aDivision of Pharmacology, Department of Internal Medicine, University of Pisa, Pisa, Italy;bDepartment of Preclinical and Clinical Pharmacology, University of Florence, Firenze, Italy |
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| Abstract: | Colorectal cancer is the second leading cause of cancer-related deaths in the world. Despite many therapeutic opportunities, prognosis remains dismal for patients with metastatic disease, and a significant portion of early-stage patients develop recurrence after chemotherapy. Epigenetic gene regulation is a major mechanism of cancer initiation and progression, through the inactivation of several tumor suppressor genes. Emerging evidence indicates that epigenetics may also play a key role in the development of chemoresistance. In the present review, we summarize epigenetic mechanisms triggering resistance to three commonly used agents in colorectal cancer: 5-fluorouracil, irinotecan and oxaliplatin. Those epigenetic biomarkers may help stratify colorectal cancer patients and develop a tailored therapeutic approach. In addition, epigenetic modifications are reversible through specific drugs: histone-deacetylase and DNA-methyl-transferase inhibitors. Preclinical studies suggest that these drugs may reverse chemoresistance in colorectal tumors. In conclusion, an epigenetic approach to colorectal cancer chemoresistance may pave the way to personalized treatment and to innovative therapeutic strategies. |
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| Keywords: | Colorectal cancer Epigenetics Chemoresistance 5-Fluorouracil Irinotecan Oxaliplatin Histone deacetylase inhibitors DNA-methyl-transferase inhibitors |
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