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.

Septin 9 hypermethylation contributes to migration and resistance to drug treatments in colon cancer

“…Multiple studies have highlighted increased resistance to chemotherapy in advanced CRC patients [21,22]. Given that septin 9 suppression is one of the early biomarker and prerequisite for CRC progression, we reasoned, if this would facilitate the development of chemoresistance in later stages.…”

Polymorphisms of cell cycle regulator genes CCND1 G870A and TP53 C215G: Association with colorectal cancer susceptibility risk in a Malaysian population

“…As a result, large numbers of research studies have been directed towards the investigation of CRC, particularly with regard to its etiology, prevention and treatment (17)(18)(19).…”

4-Acetyl-antroquinonol B Suppresses SOD2-Enhanced Cancer Stem Cell-Like Phenotypes and Chemoresistance of Colorectal Cancer Cells by Inducing hsa-miR-324 Re-Expression

“…Similarly, the cumulative evidence of the presence and implication of a small subset of the CRC bulk termed CSCs in the tumorigenicity, oncogenicity, tumor progression, and disease recurrence of CRC (6,7), further begs the case for a novel therapeutic option with CSC -targeting potentials, high curative efficacy and low drug-associated toxicity.…”