title: Epigenetics and chemoresistance in colorectal cancer: an opportunity for treatment tailoring and novel therapeutic strategies.
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.
authors.affiliation: Division of Pharmacology, Department of Internal Medicine, University of Pisa, Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Crea
authors.forename: Stefania
authors.initials: S
authors.lastname: Nobili
authors.forename: Elisa
authors.initials: E
authors.lastname: Paolicchi
authors.forename: Gabriele
authors.initials: G
authors.lastname: Perrone
authors.forename: Cristina
authors.initials: C
authors.lastname: Napoli
authors.forename: Ida
authors.initials: I
authors.lastname: Landini
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi
authors.forename: Enrico
authors.initials: E
authors.lastname: Mini
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D000077146:Irinotecan; D009364:Neoplasm Recurrence, Local; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D057285:Precision Medicine
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin