Abstract
Enumeration of circulating tumor cells (CTCs) in peripheral blood with the gold standard CellSearchTM has proven prognostic value for tumor recurrence and progression of metastatic disease. Therefore, the further molecular characterization of isolated CTCs might have clinical relevance as liquid biopsy for therapeutic decision-making and to monitor disease progression. The direct analysis of systemic cancer appears particularly important in view of the known disparity in expression of therapeutic targets as well as epithelial-to-mesenchymal transition (EMT)-based heterogeneity between primary and systemic tumor cells, which all substantially complicate monitoring and therapeutic targeting at present. Since CTCs are the potential precursor cells of metastasis, their in-depth molecular profiling should also provide a useful resource for target discovery. The present review will discuss the use of systemically spread cancer cells as liquid biopsy and focus on potential target antigens.
Highlights
Metastasis is the major cause of cancer-related death [1]
In this ongoing multi-center, randomized phase III study, metastatic breast cancer patients with initially HER2-negative primary tumors but HER2positive circulating tumor cells (CTCs) are treated with standard therapy alone or standard therapy combined with Lapatinib treatment. 711 out of 1123 HER2-negative patients enrolled in this study had measurable CTCs counts after EpCAM-mediated enrichment, and 134 patients had at least one HER2-positive CTCs in 7.5mL blood
Metastasis is the major thread for cancer patients and, despite progress in the era of molecular therapy, remains incurable in most cases
Summary
Metastasis is the major cause of cancer-related death [1]. Growing evidence supports the notion that locally invading, blood-borne circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in bone marrow and lymph nodes are precursors of recurrent tumors and metastases. EpCAM expression is dynamic and not steady as it was long assumed In this respect, antigen-independent isolation of CTCs and DTCs becomes highly relevant in order to assess and study varying phenotypes of these cells in tumor progression, recurrence, metastases formation and treatment responses. Potential benefit of targeting HER2-positive CTCs in patients is further addressed in the DETECT III study (NCT01619111) In this ongoing multi-center, randomized phase III study, metastatic breast cancer patients with initially HER2-negative primary tumors but HER2positive CTCs are treated with standard therapy alone or standard therapy combined with Lapatinib treatment (antiHER2/EGFR inhibitor). PD-L1 expression on CTCs has once more dual potential for the identification of patients likely to respond to PD treatment in the context of liquid biopsies and as therapeutic target to reactivate the immune system towards systemic cancer cells
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