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BackgroundCell-free tumor-derived DNA (ctDNA) allows non-invasive monitoring of cancers, but its utility in renal cell cancer (RCC) has not been established.MethodsHere, a combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients (n = 91) with various renal tumor subtypes, were used to determine ctDNA content in plasma and urine.ResultsOur data revealed lower plasma ctDNA levels in RCC relative to other cancers of similar size and stage, with untargeted detection in 27.5% of patients from both cohorts. A sensitive personalized approach, applied to plasma and urine from select patients (n = 22) improved detection to ~ 50%, including in patients with early-stage disease and even benign lesions. Detection in plasma, but not urine, was more frequent amongst patients with larger tumors and in those patients with venous tumor thrombus.With data from one extensively characterized patient, we observed that plasma and, for the first time, urine ctDNA may better represent tumor heterogeneity than a single tissue biopsy. Furthermore, in a subset of patients (n = 16), longitudinal sampling revealed that ctDNA can track disease course and may pre-empt radiological identification of minimal residual disease or disease progression on systemic therapy. Additional datasets will be required to validate these findings.ConclusionsThese data highlight RCC as a ctDNA-low malignancy. The biological reasons for this are yet to be determined. Nonetheless, our findings indicate potential clinical utility in the management of patients with renal tumors, provided improvement in isolation and detection approaches.

Cell-free tumour-derived DNA (ctDNA) allows non-invasive monitoring of cancers but its utility in renal cell cancer (RCC) has not been established. Here, untargeted and targeted sequencing methods, applied to two independent cohorts of renal tumour patients (n=90), were used to determine ctDNA content in plasma and urine. Our data revealed lower plasma ctDNA levels in RCC relative to other cancers, with untargeted detection of ∼33%. A sensitive personalised approach, applied to plasma and urine from select patients improved detection to ∼50%, including in patients with early-stage and even benign lesions.A machine-learning based model predicted detection, potentially offering a means of triaging samples for personalised analysis. In addition, with limited data we observed that plasma, and for the first time, urine ctDNA may better represent tumour heterogeneity than tissue biopsy. Furthermore, longitudinal sampling of >200 plasma samples revealed that ctDNA can track disease course. Additional datasets will be required to validate these findings.Overall, our data highlight RCC as a ctDNA-low malignancy, but indicate potential clinical utility provided improvement in detection approaches.One sentence summaryComplementary sequencing methods show that cell-free tumour DNA levels are low in renal cancer though, via various strategies, may still be informative.

Here resveratrol is presented through the multiple biological processes with primary relation to functions of a cancer cell. In contrast with the French paradox in which resveratrol is associated with protection against coronary heart disease, a cancer cell discrepancy is linked to a large number of experimental data without enough clinical evidence gained in clinical trials. This overview is mainly focused on tackling the molecular and pathological processes considered as important during carcinogenesis and malignant disease progression. A body of accumulating experimental evidence considering resveratrol use against cancer cells at the level of both a biological activity and a molecular mechanism is currently collected. Oncologists live in hope that resveratrol or a resveratrol-derivate characterized by more resisting against metabolizing enzymes will find a stable place in the armamentarium of anticancer agents or pharmacologically significant modifiers of other antineoplastic drugs in catholic use.