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. 2016 Sep 24;8(1):1884–1912. doi: 10.18632/oncotarget.12242

Table 1. Current molecular markers for the identification and therapeutic targeting of CTCs and DTCs in solid cancers.

Biomarker Expression rate Drug Description
Markers for CTCs
EpCAM 37-42.3% Panorex, MT201, MT101, ING-1

  • FDA-approved CellSearchTM system depends on EpCAM-specific capturing of CTCs in various cancers [21, 30, 47, 49, 125, 127, 258–262]

  • Loss of EpCAM on CTCs as a result of dynamic phenotypic changes during EMT[11, 35, 150, 151, 263]
CD44 35.2% Pan-CD44 antibody H90

  • CD44 expression in CTCs of HNSCC, breast, gastric and endometrial cancer patients [46, 264–268]
ALDH1 17.7-80% ATRA, DEAB

  • ALDH1 expression in CTCs of breast, non-small cell lung and endometrial cancer patients [36, 264, 266, 267, 269]
CD133 83% CART133 chimeric antigen receptor (CAR) T cells

  • Expression of the cancer stem cell marker CD133 in CTCs of metastatic breast, colon, colorectal, renal cell, hepatocellular and non-small cell lung cancer patients [266, 269–257]
FGF2 n.a. Dovitinib, Pentraxin-3

  • Frequent secretion of FGF2 by CTCs in pM1-staged prostate cancer [276]
KRT7, KRT18, KRT19 46.9% Anti-KRT19 antibody HPA002465

  • KRT7, 18 and 19 expression in CTCs from ovarian, gastric and gastroesophageal cancer patients [277, 278]

  • Used for therapy monitoring of advanced NSCLC and breast cancer[279]
c-Met+/CD47+ 0.8-33.3% Hu5F9-GA, ARG 197

  • CD44/c-Met/CD47 CTCs from breast cancer patients display metastatic potential [46]

  • c-Met+/CD47+ CTCs as novel independent prognosticator of OS in luminal breast cancer [154, 236]

  • c-Met as a capture antigen for CTCs and as a therapeutic target [237, 238, 280]

  • CD47 expression on CTCs of colorectal cancer [239, 281]
HER2 7.9-35.9% Herceptin, Pertuzumab, Lapatinib, Trastuzumab-mertansine (T-DM1)

  • HER2 expression on CTC of metastatic breast, non-small cell lung, gastric, gastrointestinal, ovarian cancer [12, 13, 36, 119, 178, 189, 282]

  • Anti-HER2 therapy to address HER2-positive CTCs [283]

  • HER2 is part of the signature of breast cancer CTCs competent for brain metastases [284]
EGFR 18-56% Cetuximab, Afatinib, Erlotinib, Gefitinib, Panitumumab

  • EGFR expression on CTCs of colorectal, prostate, non-small cell lung, gastric, head and neck, and breast cancer [32, 36, 121, 210, 283, 285–288]

  • Treatment resistance T790M EGFR mutation in CTCs of non-small cell lung cancer [289]

  • Lapatinib treatment of metastatic breast cancer patients with EGFR-positive CTCs [290]

  • EGFR is part of the signature of breast cancer CTCs competent for brain metastases [284]
MUC1/16 28.1-90% ASI402

  • Expression of mucin 1 and 16 in CTCs from ovarian cancer patients [277]
HPSE n.a. PI-88

  • Breast cancer CTCs express heparanase [291]

  • HER2/EGFR/HPSE/Notch1-positive breast cancer CTCs have brain metastastic potential [284]
Androgen receptor 16.3-18% Bicalutamide, Flutamide

  • Nuclear expression of androgen receptor splice variant 7 protein in CTCs of metastatic castration-resistant prostate cancer is a treatment-specific biomarker that is associated with superior survival on taxane therapy over ARS-directed therapy [288, 292]
Telomerase n.a. Imetelstat

  • Telomerase activity on CTC of metastatic prostate cancer is a prognostic marker [293]

  • Telomease-sensitive adenovirus as diagnostic and therapeutic tool against CTCs in various cancer [294, 295]
Vimentin 32.3% Withaferin-A, Silibirin, Quercetin

  • Decrease OS of castration-resistant prostate cancer patients with vimentin/ki-67-positive CTCs [296]
Ki-67 20.8-45.1% n.a.

  • Ki67 expression in CTCs of metastatic breast cancer [297, 298]
M-30 10-76.63% M30 CytoDeath™ ELISA

  • Apoptosis-related fragment of keratin 8 generated by caspases

  • Metastatic disease is associated with lower numbers of apoptotic CTCs [299]
TWIST1 n.a. Curcumin, SFN, Quercetin, CADPE, Moscatilin, NAC, BMP7, Claudins

  • TWIST1 is expressed in CTCs of breast cancer patients along with further EMT and stem cell markers [269]
uPAR n.a. PAI-1, anti-uPAR antibody 10G7, WX-UK1, Mesupron

  • Expression of uPAR on subsets of CTCs in metastasized breast cancer [300]

  • Co-amplification of HER2 and uPAR in CTCs of breast cancer [301]
Markers for DTCs
CD44 33-100% Pan-CD44 antibody H90

  • CD44 expression on most breast cancer DTCs [302]
Survivin n.a. ISIS23722, EM-1421

  • Survivin expression in bone marrow-resident DTCs in colorectal cancer [303]
TWIST1 31% Curcumin, SFN, Quercetin, CADPE, Moscatilin, NAC, BMP7, Claudins

  • TWIST1 expression in bone marrow-resident DTCs in non-metastatic breast cancer [304, 305]
uPAR 58% PAI-1, anti-uPAR antibody 10G7, WX-UK1, Mesupron

  • uPAR expression on DTCs of localized prostate cancer is an adverse prognostic marker [306]
Thomsen-Friedenreich antigen 98% JAA-F11

  • Thomsen-Friedenreich antigen is expressed on bone marrow-resident breast cancer DTCs [307]
HER2 43% Herceptin, Pertuzumab, Lapatinib, Trastuzumab-mertansine (T-DM1)

  • HER2 expression on DTCs in breast, ovarian and esophageal cancer [67, 282, 308]

  • Gain of HER2 expression in esophageal cancer DTCs confers high risk of early death [67]

  • HER2 expression on breast cancer DTCs as a prognostic marker for OS and PFS [309–311]

  • 52% concordance of HER2 expression on primary tumor and DTCs in patients with early breast cancer [312]
EGFR 15-88% Cetuximab, Afatinib, Erlotinib, Gefitinib, Panitumumab

  • EGFR expression on breast, colorectal and gastrointestinal cancer DTCs [313–315]

  • Cancer-specific EGFRvIII mutant as a marker of breast cancer DTC [316]

  • EGFR and FGF2 promote amplification of DTCs
FGF2 n.a. Dovitinib, Pentraxin-3
NUAK1 n.a. WZ4003

  • Differential expression of NUAK1, PIN4, MALT1, and CDC25B in single prostate cancer DTC defines dormant subtypes .[317]
PIN4 n.a. Anti-PIN4 antibody EPR10033
MALT1 n.a. EP603Y
CDC25B n.a. Anti-CDC25B antibody S353
CEA 0-84% n.a.

  • CEA expression on breast, colorectal, and gastric cancer DTCs [315, 318, 319]
EpCAM 28.5- Panorex, MT201, MT101, ING-1

  • Expression of EpCAM on non-small cell lung, breast, rectal, ovarian, prostate cancer DTCs [176, 317, 320–324]

  • EpCAM-positive DTCs as therapeutic targets [323]

  • Frequent loss of EpCAM expression on bone marrow-resident DTCs in esophageal cancer patients [10]

MUC: mucin; ALDH1: aldehyde dehydrogenase isoform 1;CD47: cluster of differentiation 47; EGFR: epidermal growth factor receptor; FDA: food and drug administration; EMT: epithelial-mesenchymal transition; mCRPC: metastatic castration resistant prostate cancer; HPSE; N-acetylcysteine, NAC; Caffeic acid 3,4-dihydroxy-phenethyl ester; uPAR: urokinase-type plasminogen activator receptor; MRD: minimal residual disease; CEA:carcinoembryonic antigen.

n.a.: not applicable.