Pharmacologic resistance in colorectal cancer: a review

Abstract

Colorectal cancer (CRC) persists as one of the most prevalent and deadly tumor types in both men and women worldwide. This is in spite of widespread, effective measures of preventive screening, and also major advances in treatment options. Despite advances in cytotoxic and targeted therapy, resistance to chemotherapy remains one of the greatest challenges in long-term management of incurable metastatic disease and eventually contributes to death as tumors accumulate means of evading treatment. We performed a comprehensive literature search on the data available through PubMed, Medline, Scopus, and the ASCO Annual Symposium abstracts through June 2015 for the purpose of this review. We discuss the current state of knowledge of clinically relevant mechanisms of resistance to cytotoxic and targeted therapies now in use for the treatment of CRC.

Cytotoxic Effect of Caralluma fimbriata Against Human Colon Cancer Cells

“…Due to an increasing rate of mortality associated with cancer and adverse or toxic side effects of cancer chemotherapy and radiation therapy, discovery of new anticancer agents derived from nature has begun especially plants and the screening of medicinal plants as a source of anticancer molecules. 5 There is an overwhelming evidence of a preventive/protective role of dietary plant extracts, especially fruits, vegetables, grains, and herbs, against colon cancer. Indeed, dietary intervention is emerging as an alternative to prevent the progression of colon cancer mainly due to its potency and reduced toxicity.…”

The Hdac Inhibitor Sodium Phenylbutyrate Enhances the Cytotoxicity Induced by 5-Fluorouracil, Oxaliplatin, and Irinotecan in Colorectal Cancer Cell Lines

“…Adjuvant chemotherapy consisting mainly of 5-fluorouracil, oxaliplatin, and irinotecan, has been associated with improved response rates, reduced risk of tumor recurrence and mortality, and enhanced disease-free and median survival rates [4][5][6][7][8]. Despite the advances in chemotherapy and targeted molecular agents, about 90% of patients with advanced metastatic colorectal cancer fail therapy, which is mainly attributed to resistance, either intrinsic or acquired [9,10].…”

Paricalcitol Enhances the Chemopreventive Efficacy of 5-Fluorouracil on an Intermediate-Term Model of Azoxymethane-Induced Colorectal Tumors in Rats

“…The limited therapeutic efficacy of its current chemotherapy represents the most important challenge in colorectal cancer management. With this aspect, 5-fluorouracil (5-FU)-based therapy, either alone or in combination with other cytotoxic agents (e.g., irinotecan, leucovorin, or oxaliplatin), remains the standard approach (2)(3)(4). Overall, 5-FU still exhibits limited efficacy with low tumor response rate ranging between 7% and 17 % with its monotherapy and 35%-39% when given with other chemotherapeutic agents (3,4).…”

“…With this aspect, 5-fluorouracil (5-FU)-based therapy, either alone or in combination with other cytotoxic agents (e.g., irinotecan, leucovorin, or oxaliplatin), remains the standard approach (2)(3)(4). Overall, 5-FU still exhibits limited efficacy with low tumor response rate ranging between 7% and 17 % with its monotherapy and 35%-39% when given with other chemotherapeutic agents (3,4). More importantly, although the recent addition of new targeted agents, such as bevacizumab and cetuximab, to the standard chemotherapy provides hope for more effective therapy in advanced colorectal cancer, they have shown only modest benefit and are subject to both primary and secondary resistance, like traditional chemotherapy, which ultimately leads to treatment failure (4).…”