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Galletti et al.                                                                                                                                                                                   Using CTCs in prostate cancer

           Table 2: CTC-based molecular markers investigated in prostate cancer
           Enrichment
           strategy          Biomarker   Assay      Patient cohort          Main findings         References
           Ficoll              ERG      RT-PCR   72 pts treated with taxane   Detection of TMPRSS2-ERG was   [81]
                                                  chemotherapy (50 with   significantly correlated with shorter
                                                  docetaxel and 22 with   PSA-progression free survival
                                                      cabazitaxel)
           FACS sorting         AR         IF    20 pts (10 abi-treated, 10  Increase in median AR staining intensity   [59]
                                                      abi-naïve)      in patients with prior abi exposure
                               Ki-67       IF    16 pts for AR expression  Increased AR expression and nuclear   [59]
                                                 and 10 pts for AR nuclear  localization associated with elevated Ki-
                                                      localization               67
                            Steroidogenic   RT-PCR      5 pts          Detection of AKR1C3, SRD5A1,   [82]
                              enzymes                               CYP17A1 in CTCs from pts with CRPC
           ScreenCell ®     EMT-related   RT-PCR  308 CTCs from 8 pts  Subset of EMT-related genes found   [86]
                               genes                                 in CTCs of CRPC; less frequently in
                                                                          castration-sensitive PC
           HD-CTC assay         AR         IF     27 pts (12 with NEPC,   Low or absent AR expression, lower   [87]
           (EPIC Sciences™)                       5 with atypical clinical   cytokeratin expression, and smaller
                                                  features suggestive of   morphology in CTCs from NEPC pts
                                                  NEPC, 10 with CRPC)
                               ARv7        IF    191 samples from 161 pts  Nuclear expression of ARv7 in CTCs   [69]
                                                                     associated with superior survival on
                                                                      taxane therapy over AR inhibitors
           CellSearch ®         AR         IF     Taxane treated pts: 17   13/18 (72%) of progression samples   [62]
                                                 samples from responding/ showed CTCs with nuclear AR; 12/17
                                                 stable pts; 18 samples at   (71%) of responding/stable samples
                                                      progression     showed CTCs with cytoplasmic AR
                                           IF     8 pts (baseline and at   5/8 (63%) patients showed increase   [60]
                                                  progression after abi or   median AR expression at progression
                                                        enza)
                                          FISH     9 pts with > 5 CTCs  Marked AR amplification in 5/9 (56%)   [88]
                                                                          pts (all with CTC > 50)
                                          FISH    33 pts with > 4 CTCs  28/33 (85%) pts had CTCs with < 3   [76]
                                                                     copies of AR, 10/33 (30%) with < 4-5
                                                                     copies, 15/33 (45%) with > 5 copies
                               ERG        FISH    49 pts with > 4 CTCs  ERG rearrangement in 23/49 (47%) pts   [76]
                                                                     (matched ERG gene status of tumor
                                                                           tissue in all cases)
                               PTEN       FISH    49 pts with > 4 CTCs  PTEN loss in 13/49 (27%) pts; (6/13   [76]
                                                                      (46%) pts had homozygous loss of
                                                                           PTEN in all CTCs)
                               EGFR        IF     20 pts with > 5 CTCs  18/20 (90%) pts with EGFR positive   [88]
                                                                                CTCs
           AdnaTest            ARv7     RT-PCR  62 pts (31 treated with abi,  0/18 (0%) pts with detectable levels of   [42]
                                                  31 treated with enza)  ARv7 had PSA response to either abi or
                                                                                enza
                                        RT-PCR    37 pts receiving taxane  No difference in PSA response between   [68]
                                                     chemotherapy    pts with or without detectable ARv7
           MagSweeper      Prostate-specific  RT-PCR  20 CTCs from 4 pts  19/20 (95%) of CTCs positive for at   [35]
                              markers                                least one prostate marker (AR, PSA,
                                                                            KLK3, TMPRSS2)
           EpCAM-conjugated    ERG      RT-PCR      41 pts with CTCs  TMPRSS2-ERG fusion detected in   [76]
           magnetic beads                                                  15/41 (37%) of pts
           VERSA                AR         IF    17 pts (4 treatment-naïve,   Pts responding to AR-targeted or   [47]
                                                 10 responding to therapy,  chemotherapy treatments showed lower
                                                 3 progressing on therapy) nuclear AR percentage compared to pts
                                                                              progressing
                               ARv7     RT-PCR   26 pts (19 treated with AR   ARv7 was detected in 5/7 (71%) pts   [47]
                                                   targeted therapies)  who had evidence of radiographic
                                                                     progression compared to 1/19 (5%)
                                                                     pts without evidence of radiographic
                                                                              progression
                                                                                                                                                                                                                  Continued...
                           Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ September 27, 2017     197
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