Abstract
Renal cell carcinoma is a highly malignant cancer that would benefit from non-invasive innovative markers providing early diagnosis and recurrence detection. Circulating tumor cells are a particularly promising marker of tumor invasion that could be used to improve the management of patients with RCC. However, the extensive genetic and immunophenotypic heterogeneity of cells from RCC and their trend to transition to the mesenchymal phenotype when they circulate in blood constitute a challenge for their sensitive and specific detection. This review analyzes published studies targeting CTC in patients with RCC, in the context of the biological, pathological, and molecular complexity of this particular cancer. Although further analytical and clinical studies are needed to pinpoint the most suitable approach for highly sensitive CTC detection in RCC patients, it is clear that this field can bring a relevant guide to clinicians and help to RCC patients. Furthermore, as described, a particular subtype of RCC—the ccRCC—can be used as a model to study the relationship between cytomorphological and genetic cellular markers of malignancy, an important issue for the study of CTC from any type of solid cancer.
Highlights
Renal cell carcinoma (RCC) is a very invasive and chemoresistant disease which is often treated by surgical resection as it responds poorly to radiotherapy [1]
Studies and reviews on liquid biopsy that did not concern RCC, as well as RCC studies that did not report on circulating tumor cells (CTC) were excluded from the systematic review, some are cited as reference for particular arguments within the text
Liu and colleagues used the NanoVelcro platform combined with CA9-/CD147capture antibodies to study CTC from 70 clear cell renal cell carcinoma (ccRCC) patients [24]
Summary
Renal cell carcinoma (RCC) is a very invasive and chemoresistant disease which is often treated by surgical resection as it responds poorly to radiotherapy [1]. Available targeted therapies for metastatic RCC, such as immune checkpoint inhibitors, mTOR inhibitors, or VEGF tyrosine kinase inhibitors, are routinely administered in clinical practice, yet no predictive biomarkers are used to guide the selection of those targeted treatments [5]. In this context, there is an urgent need for reliable biomarkers of RCC, enabling early diagnosis, prognosis, and monitoring of treatment efficacy and potential relapse of the disease. Analysis of ctDNA presents as a straightforward approach for genetic assessment of the tumor burden (for a comprehensive review of the role of ctDNA in the management of RCC, please refer to [11]). Few studies have reported on CTC analysis in the context of RCC
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