Development and Application of Liquid Biopsies in Metastatic Prostate Cancer

Abstract

Technologies for analysis of circulating tumor cells (CTCs) continue to evolve rapidly, and the latest high content scanning platforms have underscored the phenotypic heterogeneity of CTC populations. Among liquid biopsies, CTC enumeration remains the most extensively validated prognostic marker to date, but other clinically relevant phenotypes like androgen receptor (AR) localization or presence of AR-V7 splice variant are important new predictors of therapy response. Serial genomic profiling of CTCs or circulating tumor DNA (ctDNA) is helping to define primary and acquired resistance mechanisms and helping to guide patient selection for targeted therapies such as poly(adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibition. The era of liquid biopsy-based biomarkers has arrived, driven by powerful new enrichment and analysis techniques. As new blood-based markers are identified, their biological significance as disease drivers must be elucidated to advance new therapeutic strategies, and their clinical impact must be translated through assay standardization, followed by analytical and clinical validation. These efforts, already ongoing on multiple fronts, constitute the critical steps toward more effective precision management of advanced prostate cancer.

Dynamics of the cell-free DNA methylome of metastatic prostate cancer during androgen-targeting treatment

“…This is particularly advantageous for mCRPC, as most patients have had prior radical prostatectomy and bone metastases are often inaccessible. Numerous studies have explored the potential of circulating tumor cell (CTC) or circulating nucleic acid markers in mCRPC (18). Counting the number of CTCs and/or characterization of molecular alterations (i.e.…”

“…Liquid biopsies are emerging as a minimally invasive source of biomarkers, reflecting tumor turnover (18). Numerous studies have explored the potential of circulating tumor cell (CTC) or circulating nucleic acid markers in mCRPC (19). Counting the number of CTCs and/or characterization of molecular alterations (i.e.…”

The Innovations, Advances and Outlooks of Liquid Biopsy in Oncology: A Literature Review

“…Advances in the understanding of molecular biology of cancer have led to the development of the Liquid Biopsy, which is a revolutionary new and reproducible technique, serving for the early detection of malignant neoplasms, as well as for the initiation of personalized and precise treatment, analysis of treatment response in real time, in addition to the prognosis of patients. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] This tool is currently called the Net Biopsy and uses the detection of biomarkers of cancer cells, such as circulating tumor cells (CTCs), circulating cell DNA (cfDNA), DNA of tumor cells (ctDNA) and exosomes, which can be detected in various fluids, such as blood, plasma and serum, urine, saliva and cerebrospinal fluid (CSF) . [2][3][4][5][6][7][8][9][10][11] This new diagnostic technique can be performed non-invasively or minimally invasive and may offer many advantages over conventional tissue biopsies.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] This tool is currently called the Net Biopsy and uses the detection of biomarkers of cancer cells, such as circulating tumor cells (CTCs), circulating cell DNA (cfDNA), DNA of tumor cells (ctDNA) and exosomes, which can be detected in various fluids, such as blood, plasma and serum, urine, saliva and cerebrospinal fluid (CSF) . [2][3][4][5][6][7][8][9][10][11] This new diagnostic technique can be performed non-invasively or minimally invasive and may offer many advantages over conventional tissue biopsies. [1][2][3][4]6,7,[10][11][12][13][14][15][16][17][18][19][20] This new technology can develop a new concept of individualized or personalized therapy...…”

“…[2][3][4][5][6][7][8][9][10][11] This new diagnostic technique can be performed non-invasively or minimally invasive and may offer many advantages over conventional tissue biopsies. [1][2][3][4]6,7,[10][11][12][13][14][15][16][17][18][19][20] This new technology can develop a new concept of individualized or personalized therapy, favoring an understanding that the same type of cancer and in the same stage of disease may have different treatments in different patients, because the liquid biopsy may also verify the heterogeneity and some types of tumor mutations and resistance to some types of drugs used in chemotherapy. 2,4,5,8,9,17 This approach, however, requires the development of reliable biomarkers and biosensors.…”