title: Chemoprevention, chemotherapy, and chemoresistance in colorectal cancer.
abstract: Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in industrialized countries. Chemoprevention is a promising approach, but studies demonstrating their usefulness in large populations are still needed. Among several compounds with chemopreventive ability, cyclooxygenase inhibitors have received particular attention. However, these agents are not without side effects, which must be weighed against their beneficial actions. Early diagnosis is critical in the management of CRC patients, because, in early stages, surgery is curative in >90% of cases. If diagnosis occurs at stages II and III, which is often the case, neoadjuvant chemotherapy and radiotherapy before surgery are, in a few cases, recommended. Because of the high risk of recurrence in advanced cancers, chemotherapy is maintained after tumor resection. Chemotherapy is also indicated when the patient has metastases and in advanced cancer located in the rectum. In the last decade, the use of anticancer drugs in monotherapy or in combined regimens has markedly increased the survival of patients with CRC at stages III and IV. Although the rate of success is higher than in other gastrointestinal tumors, adverse effects and development of chemoresistance are important limitations to pharmacological therapy. Genetic profiling regarding mechanisms of chemoresistance are needed to carry out individualized prediction of the lack of effectiveness of pharmacological regimens. This would minimize side effects and prevent the selection of aggressive, cross-resistant clones, as well as avoiding undesirable delays in the use of the most efficient therapeutic approaches to treat these patients.
authors.affiliation: Department of Physiology and Pharmacology, University of Salamanca, CIBERehd, Salamanca, Spain. jjgmarin@usal.es
authors.forename: Jose J G
authors.initials: JJ
authors.lastname: Marin
authors.forename: Fermin
authors.initials: F
authors.lastname: Sanchez de Medina
authors.forename: Beatriz
authors.initials: B
authors.lastname: Castaño
authors.forename: Luis
authors.initials: L
authors.lastname: Bujanda
authors.forename: Marta R
authors.initials: MR
authors.lastname: Romero
authors.forename: Olga
authors.initials: O
authors.lastname: Martinez-Augustin
authors.forename: Rosario Del
authors.initials: RD
authors.lastname: Moral-Avila
authors.forename: Oscar
authors.initials: O
authors.lastname: Briz
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018890:Chemoprevention / Q000379:methods; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000517:prevention & control*; D011322:Primary Prevention / Q000379:methods; D055502:Secondary Prevention / Q000379:methods
chemical_list: D016588:Anticarcinogenic Agents; D016861:Cyclooxygenase Inhibitors