Department of Physiology and Pharmacology, University of Salamanca, CIBERehd, Salamanca, Spain.
Drug Metab Rev. 2012 May;44(2):148-72. doi: 10.3109/03602532.2011.638303.
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.
结直肠癌（CRC）是第三大常见癌症，也是工业化国家癌症相关死亡的第二大主要原因。化学预防是一种很有前途的方法，但仍需要研究证明其在大人群中的有效性。在具有化学预防能力的几种化合物中，环氧化酶抑制剂受到了特别关注。然而，这些药物并非没有副作用，必须权衡其有益作用。早期诊断对于 CRC 患者的治疗至关重要，因为在早期阶段，手术在 >90%的病例中是治愈性的。如果在 II 期和 III 期诊断，这通常是情况，手术前的新辅助化疗和放疗在少数情况下是推荐的。由于晚期癌症复发风险高，在肿瘤切除后仍需进行化疗。当患者有转移灶或位于直肠的晚期癌症时，也需要化疗。在过去十年中，单药或联合方案中抗癌药物的使用显著提高了 III 期和 IV 期 CRC 患者的生存率。尽管成功率高于其他胃肠道肿瘤，但不良反应和化疗耐药性的发展是药物治疗的重要限制。需要进行化学耐药机制的基因分析，以对药物治疗方案的无效进行个体化预测。这将最大限度地减少副作用，防止选择侵袭性、交叉耐药克隆，并避免对这些患者使用最有效治疗方法的不必要延迟。
