Currently, metastatic colon cancer is treated with monotherapeutic regimens such as folinic acid, fluorouracil, and oxaliplatin (FOLFOX), capecitabine and oxaliplatin (CapeOX), and leucovorin, fluorouracil, and irinotecan hydrochloride (FOLFIRI). Other treatments include biological therapies and immunotherapy with drugs such as bevacizumab, panitumumab, cetuximab, and pembrolizumab. After the research, it was found that some mutations make those treatments not as effective in all patients. In this bibliographic review, we investigated the pharmacogenetic explanations for how mutations in the genes coding for rat sarcoma virus (RAS) and rapidly accelerated fibrosarcoma (RAF) reduce the effectiveness of these treatments and allow the continued proliferation of tumors. Furthermore, we note that patients with mutations in the dihydropyrimidine dehydrogenase (DPDY) gene usually require lower doses of therapies such as 5-fluorouracyl (5-FU) and capecitabine to avoid severe adverse effects. Some other mutations in the thymidylate synthase gene (TSYM), methylenetetrahydrofolate reductase gene (MTHFR), and ATP binding cassette transporter B (ABCB1 and ABCB2) affect efficacy and security of the treatments. It is important to address the clinical implication of the oncologist in the study of gene mutations than can influence in the antitumoral response and safety of colon cancer treatments.

Although long-term smoking has been associated with chronic kidney disease, its effect on kidney function in early stages has not been clarified. Therefore, the proposed objectives were: (1) to identify subclinical kidney damage in smokers, through a panel of biomarkers; (2) to evaluate the progression of subclinical kidney damage after two years of consumption in these patients; and (3) study whether quitting smoking reduces kidney damage. A prospective study was carried out (patients recruited from a primary care centre and a clinical smoking unit). Kidney function was assessed using a panel of biomarkers and compared between smokers and non-smokers, taking into account potential risk factors for kidney damage. These results show, for the first time in the literature, the relationship between smoking and early (subclinical) kidney damage and provide a panel of biomarkers capable of detecting this condition (Neutrophil gelatinase-associated lipocalin, Kidney injury molecule-1, N-acetyl-beta-D-glucosaminidase, transferrin, and ganglioside-activating protein GM2). This study also indicates that subclinical damage is maintained when use continues, but can be reversed if patients stop smoking. The use of these biomarkers as diagnostic tools can be a preventive measure in the development of chronic kidney disease associated with smoking and in the prevention of acute events associated with potentially nephrotoxic pharmacological treatment in smokers. Trial registration number: NCT03850756.

Background and Aims Drug nephrotoxicity is a serious medical and economic concern. In fact, 25% of the 100 most used drugs in intensive care units are toxic to the kidney, which limits their use and, therefore, the correct therapy for the patient. The administration of contrast media (CM) during diagnostic tests or surgical interventions carries the risk of contrast-induced nephropathy (CIN), which is a clinical condition defined as an increase in plasma creatinine of 25% or 0.5 mg/dL above baseline within 3-5 days after administration. Because once installed CIN has no treatment, identification of new biomarkers predicting patients at risk of CIN before receiving CM may be crucial to prevent future kidney complications. Clinical studies conducted in other medical areas have identified new urinary biomarkers, such as insulin like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases 2 (TIMP2), that anticipate the risk of developing kidney damage after the administration of different potentially nephrotoxic compounds. The objective of this work was to evaluate the usefulness of these biomarkers to predict CIN in cardiac patients. Method A clinical study was carried out with 154 patients from the University Hospital of Salamanca Cardiology Department who subsequently received a CM. Prior to contrast administration, urine samples were collected. In addition, their plasma creatinine level was registered for the following 5 days to evaluate the development of CIN. Patients were divided into Controls (who did not develop CIN) and Cases (who developed CIN). IGFBP7 and TIMP2 biomarkers were quantified in urine samples by ELISA. Subsequently, the differences between both groups were evaluated using the Mann-Whitney U test and the diagnostic capacity of each biomarker was analyzed through the generation of its receiver operating characteristic (ROC) curve. Results Of the total number of patients, 123 were assigned to the Controls group and 31 to the Cases group. In both groups the distribution of sex and risk factors was similar, except for the case of age and body mass index, which was slightly lower and higher, respectively, in the Controls group. IGFBP7 was significantly higher in Cases (p < 0.01) compared to the Controls, and the IGFBP7 x TIMP2 product further improved this significance (p < 0.001). Specifically, the area under the ROC curve for IGFBP7 was 0.67 (95% confidence interval of 0.56-0.78); while that for IGFBP7 x TIMP2 increased to 0.73 (with a 95% confidence interval of 0.63-0.84). In contrast, TIMP2 alone showed no differences between both groups of patients. Conclusion The biomarkers IGFBP7 and IGFBP7 x TIMP2 could therefore be used for the prophylactic identification and management of patients at risk of developing CIN.