Page 206 - Read Online

Galletti et al. Using CTCs in prostate cancer

Enrichment Biomarker Assay Patient cohort Main findings References
strategy
RosetteSep™ CD45 PTEN aCGH 1 pt derived organoid from Homozygous loss of PTEN [55]
depletion CTCs (MSK-PCa5)
RB1 aCGH 1 pt derived organoid from Heterozygous loss of RB1 [55]
CTCs (MSK-PCa5)
TP53 aCGH 1 pt derived organoid from Heterozygous loss of TP53 [55]
CTCs (MSK-PCa5)
CD45 depletion AR variants RT-PCR 73 samples from 46 pts ARv7 in 50/73 (68%) and ARv567s [70]
in 23/73 (32%) of samples; strong
association of ARv positivity with a
history of second line hormonal therapy
Collagen-adhesion Genome aCGH 3 pts with matched CTC and Greater percentage of genome [89]
matrix fractionation aberrances WBC DNA samples (2 pts aberrance in CTCs compared to WBC;
with matched primary tumor similar genome aberrance in CTCs and
sample) primary tumors
GEDI Chip AR IF 26 taxane treated pts with Pts who experienced PSA response [63]
available CTCs at C1D1 and had lower CTC-AR nuclear after only
C1D8 one week of treatment localization than
pts who did not respond
ERG IF 2 pts (1 ERG+ and 1 ERG-) CTCs of ERG-pt showed increase in [80]
taxane induced microtubule bundling
when treated ex-vivo with docetaxel or
cabazitaxel whereas CTCs of ERG+ pt
showed no microtubule changes
HB-Chip AR IF 4 ADT-naïve pts with ADT-naïve pts with metastatic PC [61]
metastatic PC; 17 pts had a majority of CTCs with “AR-on”
treated with abi phenotype and initiation of ADT led
to conversion to a “AR-off” within 3
months; 4/17 (24%) pts treated with abi
showed a decrease in “AR-on” CTCs;
CRPC pts had mixed phenotypes
ERG RT-PCR 2 pts with matched primary TMPRSS2-ERG fusion in CTCs of pt [44]
tumors with translocation in primary tumor; no
TMPRSS2-ERG in CTCs from patient
without fusion in primary tumor
CTC iChip AR expression RNA-seq 77 CTCs from 13 pts AR transcript in 60/77 (78%) of CTCs [57]
from 12/13 (92%) patients
AR T877A RNA-seq 77 CTCs from 13 pts T877A mutation in 5/9 (56%) CTCs [57]
mutation from 1/13 (8%) pts
ARv RNA-seq 77 CTCs from 13 pts 33/73 (43%) CTCs with at least one [57]
ARv: 26/73 (36%) CTCs with ARv7;
18/73 (25%) CTCs with ARv567es; 7/73
(10%) CTCs expressed ARv1, ARv3, or
ARv4
Wnt RNA-seq 77 CTCs from 13 pts Enrichment for non-canonical Wnt [57]
signaling in patients who progressed on
enza
CTC: circulating tumor cell; RT-PCR: real time polymerase chain reaction; IF: immunofluorescence; AR: androgen receptor; EMT:
epithelial-mesenchymal transition; pts: patients; abi: abiraterone acetate; enza: enzalutamide; WBC: white blood cell; HD: high definition;
HB: herringbone; GEDI: geometrically enhanced differential immunocapture; aCGH: array-based comparative genomic hybridization
nuclear AR expression at progression compared with to treatment generally had lower AR expression and
the pre-treatment assessment. lower percentage of AR in the nucleus.

Sperger et al. evaluated AR expression and Miyamoto et al. [61] explored AR signaling activity
[47]
subcellular localization in CTCs isolated from in CTCs isolated from PC patients, by using an
17 patients with CRPC using an EpCAM-based EpCAM-based herringbone microfluidic device, and
enrichment embedded in the VERSA device. They observed that AR-dependent pathway was active
found that patients responding to AR targeted
therapies or docetaxel-based chemotherapy showed in untreated patients, became inactive after ADT,
lower percentages of AR in the nucleus compared and could be reactivated at the time of progression,
to patients who progressed on treatment. When supporting CTCs as a dynamic biomarker that could
combining single cell data points from multiple patients, reflect the drug-induced changes of the therapeutic
they also showed that CTCs from patients responding target in real time.
198 Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ September 27, 2017