oa Editorial [Hot Topic: Biomarkers of Chemotherapeutics Efficacy and Toxicity in Colorectal Cancer (Guest Editor: Amalia Azzariti)]

For several years, 5-fluorouracil (5-FU) has represented the backbone in the majority of regiments for colorectal cancer (CRC) treatment; thanks to the introduction in the clinical practice of new drugs such as irinotecan and oxaliplatin and modern biological drugs such as bevacizumab and cetuximab the treatment of CRC evolved substantially during the past decade. Despite this progress, many questions remain unsolved highlighting the urgent need to identify predictor factors of response and toxicity that could help clinicians in selecting patients to be treated with these drugs in order to obtain better treatment responses. In this issue, our aim was to provide readers a critical and updated review of data regarding the status of treatment with chemotherapeutics or biological agents and possible predictor factors of response and toxicity that can give a general view of therapeutic options in selected populations of CRC patients. The issue starts with Gnoni et al. analysis of the pharmacokinetic and metabolism determinants of oxaliplatin and fluoropyrimidines activity in treatment of colorectal patients. They reported, through an extensive revision of literature data, that predictive markers of these “ancient” drugs effectiveness and toxicity are thymidylate synthase, dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase, methylenetetrahydrofolate reductase, deoxyuridine triphosphate nucleotidohydrolase and microsatellite instability for fluoropyrimidines and excision repair cross-complementation group 1, X-ray cross-complementing group 1, xeroderma pigmentosum group D and glutathione Stransferase for oxaliplatin. Di Paolo et al. critically revised clinical pharmacology and pharmacogenetics of irinotecan enlightening that more than cellular markers also genetic polymorphisms seem to offer a more reliable and safer approach for the identification of patients at risk...... In recent years, target therapy has been validated in the treatment of CRC patients; in their report, Caraglia et al. revised the effectiveness and reliable markers of efficacy and toxicity for drugs acting on EGFR and VEGF pathways. A deepening on the relevance of genetic aberrations underlying CRC development has been provided by Leon et al. and Yi and Tang who summarized updated insights pointing out a correlation between DNA copy-number profiles and response to fluoropyrimidine-based regimens and the relationship between imbalance alternative splicing with cancer, respectively. Moreover, Porcelli et al. reported that while folate supplementation is an essential part of several current chemotherapeutic regimens the increasing folate fortification of population may interfere with the effectiveness of chemotherapeutics. In their review, the authors reported the cellular and molecular mechanisms of cellular adaptation to folate status that may alter the pharmacology of chemotherapeutics mainly used in the treatment of CRC pointing out the importance of a preliminary evaluation of folate in tissue and blood of patients to maximize treatment efficacy while reducing a long-term impact on drug resistance. Finally, stressing the concept that chemotherapy could be responsible for MultiDrug Resistance through the involvement of ABC transporters, Colabufo et al. revised literature data on the possibility to use ABC transporters' ligands as PET radiotracers, emphasizing the dual role of these compounds as drugs and radiotracers. I and all authors involved in the preparation of this issue hope that it could be a useful tool for updating on the current biomarkers of chemotherapeutics efficacy and toxicity in CRC and we wish “good reading” to all. I think that a special thanks is due to our reviewers for their strong effort.