Home LiteratureArticle Details
PMID: 20046569 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Antibodies targeting cancer stem cells: a new paradigm in immunotherapy?

mAbs ·Vol. 1 ·No. 1 ·2009-00-00 ·Pages 12-25

Deonarain MP, Kousparou CA, Epenetos AA

Abstract

Antibody targeting of cancer is showing clinical and commercial success after much intense research and development over the last 30 years. They still have the potential to delivery long-term cures but a shift in thinking towards a cancer stem cell (CSC) model for tumor development is certain to impact on how antibodies are selected and developed, the targets they bind to and the drugs used in combination with them. CSCs have been identified from many human tumors and share many of the characteristics of normal stem cells. The ability to renew, metabolically or physically protect themselves from xenobiotics and DNA damage and the range of locomotory-related receptors expressed could explain the observations of drug resistance and radiation insensitivity leading to metastasis and patient relapse.Targeting CSCs could be a strategy to improve the outcome of cancer therapy but this is not as simple as it seems. Targets such as CD133 and EpCAM/ESA could mark out CSCs from normal cells enabling specific intervention but indirect strategies such as interfering with the establishment of a supportive niche through anti-angiogenic or anti-stroma therapy could be more effective.This review will outline the recent discoveries for CSCs across the major tumor types highlighting the possible molecules for intervention. Examples of antibody-directed CSC therapies and the outlook for the future development of this emerging area will be given.

Keywords
antibody cancer stem cell targeting therapy
MeSH Terms
Animals Antibodies, Monoclonal/immunology,therapeutic use Antibody Specificity Antigens, Neoplasm/immunology Antigens, Surface/immunology Biomarkers, Tumor/immunology Humans Neoplasms/therapy Neoplastic Stem Cells/immunology,metabolism Receptors, Cell Surface/immunology Signal Transduction/immunology
Chemicals
Antibodies, Monoclonal Antigens, Neoplasm Antigens, Surface Biomarkers, Tumor Receptors, Cell Surface
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Deonarain Mahendra P
Division of Cell and Molecular Biology, Department of Life Sciences, Imperial College London, London, UK. m.deonarain@imperial.ac.uk
Kousparou Christina A
Epenetos Agamemnon A
References (169)
169 references, click to expand
  1. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response.
    Nature. 2006 Dec 7;444(7120):756-60 PMID: 17051156
  2. Recombinant protein expression for therapeutic applications.
    Curr Opin Biotechnol. 2002 Apr;13(2):117-23 PMID: 11950561
  3. Antibody-directed enzyme prodrug therapy (ADEPT) for cancer.
    Expert Opin Biol Ther. 2004 Nov;4(11):1777-89 PMID: 15500406
  4. Inhibition of alpha(v)beta3 integrin reduces angiogenesis, bone turnover, and tumor cell proliferation in experimental prostate cancer bone metastases.
    Clin Exp Metastasis. 2003;20(5):413-20 PMID: 14524530
  5. A phase I study with adecatumumab, a human antibody directed against epithelial cell adhesion molecule, in hormone refractory prostate cancer patients.
    Eur J Cancer. 2006 Oct;42(15):2530-8 PMID: 16930989
  6. The CXCR4 chemokine receptor in acute and chronic leukaemia: a marrow homing receptor and potential therapeutic target.
    Br J Haematol. 2007 May;137(4):288-96 PMID: 17456052
  7. Specific T helper cell requirement for optimal induction of cytotoxic T lymphocytes against major histocompatibility complex class II negative tumors.
    J Exp Med. 1998 Mar 2;187(5):693-702 PMID: 9480979
  8. Location, location, location: the cancer stem cell niche.
    Cell Stem Cell. 2007 Dec 13;1(6):607-11 PMID: 18371402
  9. Potent antibody therapeutics by design.
    Nat Rev Immunol. 2006 May;6(5):343-57 PMID: 16622479
  10. Targeted therapy for cancer stem cells: the patched pathway and ABC transporters.
    Oncogene. 2007 Feb 26;26(9):1357-60 PMID: 17322922
  11. Integrin trafficking and its role in cancer metastasis.
    Cancer Metastasis Rev. 2007 Dec;26(3-4):567-78 PMID: 17786537
  12. Phase I study of cetuximab, erlotinib, and bevacizumab in patients with advanced solid tumors.
    Cancer Chemother Pharmacol. 2009 May;63(6):1065-71 PMID: 18795291
  13. Wnt/beta-catenin signaling in development and disease.
    Cell. 2006 Nov 3;127(3):469-80 PMID: 17081971
  14. Continuous cultures of fused cells secreting antibody of predefined specificity.
    Nature. 1975 Aug 7;256(5517):495-7 PMID: 1172191
  15. Aberrant activation of notch signaling in human breast cancer.
    Cancer Res. 2006 Feb 1;66(3):1517-25 PMID: 16452208
  16. CD133 expression is an independent prognostic marker for low survival in colorectal cancer.
    Br J Cancer. 2008 Oct 21;99(8):1285-9 PMID: 18781171
  17. Targeting of CD44 eradicates human acute myeloid leukemic stem cells.
    Nat Med. 2006 Oct;12(10):1167-74 PMID: 16998484
  18. Co-expression of the toleragenic glycoprotein, CD200, with markers for cancer stem cells.
    Biochem Biophys Res Commun. 2007 Dec 28;364(4):778-82 PMID: 17964286
  19. Phenotypic characterization of human colorectal cancer stem cells.
    Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10158-63 PMID: 17548814
  20. Beta1 integrin inhibition dramatically enhances radiotherapy efficacy in human breast cancer xenografts.
    Cancer Res. 2008 Jun 1;68(11):4398-405 PMID: 18519702
  21. Antibodies selected from combinatorial libraries block a tumor antigen that plays a key role in immunomodulation.
    Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):1041-6 PMID: 16418292
  22. Integrins: signaling, disease, and therapy.
    Int J Radiat Biol. 2007 Nov-Dec;83(11-12):743-51 PMID: 17852562
  23. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer.
    Nat Clin Pract Oncol. 2006 May;3(5):269-80 PMID: 16683005
  24. Leukaemia stem cells and the evolution of cancer-stem-cell research.
    Nat Rev Cancer. 2005 Apr;5(4):311-21 PMID: 15803157
  25. Invincible, but not invisible: imaging approaches toward in vivo detection of cancer stem cells.
    J Clin Oncol. 2008 Jun 10;26(17):2901-10 PMID: 18539971
  26. Tumor targeting properties of monoclonal antibodies with different affinity for target antigen CD44V6 in nude mice bearing head-and-neck cancer xenografts.
    Int J Cancer. 2002 May 20;99(3):396-402 PMID: 11992408
  27. Brain tumor stem cells: bringing order to the chaos of brain cancer.
    J Clin Oncol. 2008 Jun 10;26(17):2916-24 PMID: 18539973
  28. A phase I dose escalation study with anti-CD44v6 bivatuzumab mertansine in patients with incurable squamous cell carcinoma of the head and neck or esophagus.
    Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6064-72 PMID: 17062682
  29. The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation.
    J Natl Cancer Inst. 2006 Dec 20;98(24):1777-85 PMID: 17179479
  30. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells.
    Nature. 2006 Dec 7;444(7120):761-5 PMID: 17151667
  31. Specific association of human telomerase activity with immortal cells and cancer.
    Science. 1994 Dec 23;266(5193):2011-5 PMID: 7605428
  32. Antibody cocktails: next-generation biopharmaceuticals with improved potency.
    Trends Biotechnol. 2007 Sep;25(9):390-4 PMID: 17681390
  33. Reshaping human antibodies for therapy.
    Nature. 1988 Mar 24;332(6162):323-7 PMID: 3127726
  34. Selecting and screening recombinant antibody libraries.
    Nat Biotechnol. 2005 Sep;23(9):1105-16 PMID: 16151404
  35. Role of prostate stem cell antigen in prostate cancer research.
    Curr Opin Urol. 2002 Sep;12(5):401-6 PMID: 12172427
  36. Combining targeted agents: blocking the epidermal growth factor and vascular endothelial growth factor pathways.
    Clin Cancer Res. 2006 Jul 15;12(14 Pt 2):4421s-4425s PMID: 16857821
  37. Prospective identification of tumorigenic breast cancer cells.
    Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8 PMID: 12629218
  38. CD44 in cancer progression: adhesion, migration and growth regulation.
    J Mol Histol. 2004 Mar;35(3):211-31 PMID: 15339042
  39. BMI-1 is highly expressed in M0-subtype acute myeloid leukemia.
    Int J Hematol. 2005 Jul;82(1):42-7 PMID: 16105758
  40. MFG-E8/lactadherin promotes tumor growth in an angiogenesis-dependent transgenic mouse model of multistage carcinogenesis.
    Cancer Res. 2007 Jul 15;67(14):6777-85 PMID: 17638889
  41. Antibody constructs in cancer therapy: protein engineering strategies to improve exposure in solid tumors.
    Cancer. 2007 Jan 15;109(2):170-9 PMID: 17154393
  42. Interleukin-4 enhances proliferation of human pancreatic cancer cells: evidence for autocrine and paracrine actions.
    Br J Cancer. 2005 Mar 14;92(5):921-8 PMID: 15714203
  43. Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis.
    J Clin Oncol. 2008 Jun 10;26(17):2839-45 PMID: 18539962
  44. Identification and expansion of human colon-cancer-initiating cells.
    Nature. 2007 Jan 4;445(7123):111-5 PMID: 17122771
  45. Anti-beta1 integrin antibody reduces surgery-induced adhesion of colon carcinoma cells to traumatized peritoneal surfaces.
    Ann Surg. 2008 Jan;247(1):85-94 PMID: 18156927
  46. Targeting cancer stem cells through L1CAM suppresses glioma growth.
    Cancer Res. 2008 Aug 1;68(15):6043-8 PMID: 18676824
  47. Recombinant antibodies for cancer therapy.
    Expert Opin Biol Ther. 2008 Aug;8(8):1123-41 PMID: 18613764
  48. Edrecolomab alone or in combination with fluorouracil and folinic acid in the adjuvant treatment of stage III colon cancer: a randomised study.
    Lancet. 2002 Aug 31;360(9334):671-7 PMID: 12241873
  49. Stem cell niche: structure and function.
    Annu Rev Cell Dev Biol. 2005;21:605-31 PMID: 16212509
  50. Anti-PSCA mAbs inhibit tumor growth and metastasis formation and prolong the survival of mice bearing human prostate cancer xenografts.
    Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2658-63 PMID: 11226295
  51. Current status and issues in cancer stem cell study.
    Cancer Invest. 2008 Aug;26(7):741-55 PMID: 18608212
  52. Cancer genes and the pathways they control.
    Nat Med. 2004 Aug;10(8):789-99 PMID: 15286780
  53. Immune modulation by melanoma and ovarian tumor cells through expression of the immunosuppressive molecule CD200.
    Cancer Immunol Immunother. 2008 Jul;57(7):987-96 PMID: 18060403
  54. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell.
    Nat Med. 1997 Jul;3(7):730-7 PMID: 9212098
  55. Ligation of the CD44 adhesion molecule reverses blockage of differentiation in human acute myeloid leukemia.
    Nat Med. 1999 Jun;5(6):669-76 PMID: 10371506
  56. Lessons from multidisciplinary translational trials on anti-angiogenic therapy of cancer.
    Nat Rev Cancer. 2008 Apr;8(4):309-16 PMID: 18337733
  57. Opinion: the origin of the cancer stem cell: current controversies and new insights.
    Nat Rev Cancer. 2005 Nov;5(11):899-904 PMID: 16327766
  58. Adhesion molecules and tumor cell interaction with endothelium and subendothelial matrix.
    Cancer Metastasis Rev. 1992 Nov;11(3-4):353-75 PMID: 1423822
  59. Tumour biological aspects of CD24, a mucin-like adhesion molecule.
    J Mol Histol. 2004 Mar;35(3):255-62 PMID: 15339045
  60. Targeted photodynamic therapy with multiply-loaded recombinant antibody fragments.
    Int J Cancer. 2008 Mar 1;122(5):1155-63 PMID: 17973256
  61. Anti-Dll4 therapy: can we block tumour growth by increasing angiogenesis?
    Trends Mol Med. 2007 Sep;13(9):389-95 PMID: 17822956
  62. New immunotoxins targeting CD123, a stem cell antigen on acute myeloid leukemia cells.
    J Immunother. 2007 Sep;30(6):607-13 PMID: 17667524
  63. A perivascular niche for brain tumor stem cells.
    Cancer Cell. 2007 Jan;11(1):69-82 PMID: 17222791
  64. The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer.
    Trends Mol Med. 2008 Mar;14(3):109-19 PMID: 18261959
  65. The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst 33342 and is overexpressed in hematopoietic stem cells.
    Clin Cancer Res. 2002 Jan;8(1):22-8 PMID: 11801536
  66. Identification of human brain tumour initiating cells.
    Nature. 2004 Nov 18;432(7015):396-401 PMID: 15549107
  67. Cancer stem cells in head and neck squamous cell cancer.
    J Clin Oncol. 2008 Jun 10;26(17):2871-5 PMID: 18539966
  68. The many facets of Notch ligands.
    Oncogene. 2008 Sep 1;27(38):5148-67 PMID: 18758484
  69. ALDH1 as a functional marker of cancer stem and progenitor cells.
    Stem Cells Dev. 2009 Jan-Feb;18(1):17-25 PMID: 18573038
  70. The distribution of secondary growths in cancer of the breast. 1889.
    Cancer Metastasis Rev. 1989 Aug;8(2):98-101 PMID: 2673568
  71. Targeting, imaging, and therapy using a humanized antiprostate stem cell antigen (PSCA) antibody.
    J Immunother. 2007 May-Jun;30(4):396-405 PMID: 17457214
  72. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome.
    Cell Stem Cell. 2007 Nov;1(5):555-67 PMID: 18371393
  73. Imaging tumors with an albumin-binding Fab, a novel tumor-targeting agent.
    Cancer Res. 2007 Jan 1;67(1):254-61 PMID: 17210705
  74. CD24 affects CXCR4 function in pre-B lymphocytes and breast carcinoma cells.
    J Cell Sci. 2006 Jan 15;119(Pt 2):314-25 PMID: 16390867
  75. Catumaxomab, a rat/murine hybrid trifunctional bispecific monoclonal antibody for the treatment of cancer.
    Curr Opin Mol Ther. 2008 Jun;10(3):273-84 PMID: 18535935
  76. Biological activity of two humanized antibodies against two different breast cancer antigens and comparison to their original murine forms.
    Cancer Res. 1995 Dec 1;55(23 Suppl):5852s-5856s PMID: 7493359
  77. Pharmacokinetic and safety study of subcutaneously administered weekly ING-1, a human engineere monoclonal antibody targeting human EpCAM, in patients with advanced solid tumors.
    Ann Oncol. 2007 Oct;18(10):1704-7 PMID: 17693421
  78. Identification of cells initiating human melanomas.
    Nature. 2008 Jan 17;451(7176):345-9 PMID: 18202660
  79. Prospective identification of tumorigenic prostate cancer stem cells.
    Cancer Res. 2005 Dec 1;65(23):10946-51 PMID: 16322242
  80. A role for Wnt signalling in self-renewal of haematopoietic stem cells.
    Nature. 2003 May 22;423(6938):409-14 PMID: 12717450
  81. The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells.
    Blood. 2005 Jun 1;105(11):4163-9 PMID: 15687234
  82. Brain micro-ecologies: neural stem cell niches in the adult mammalian brain.
    Philos Trans R Soc Lond B Biol Sci. 2008 Jan 12;363(1489):123-37 PMID: 17322003
  83. The effect of anti-CD44 monoclonal antibodies on differentiation and proliferation of human acute myeloid leukemia cells.
    Leuk Lymphoma. 2004 Aug;45(8):1501-10 PMID: 15370200
  84. Telomerase and cancer therapeutics.
    Nat Rev Cancer. 2008 Mar;8(3):167-79 PMID: 18256617
  85. Anti-patched-1 antibodies suppress hedgehog signaling pathway and pancreatic cancer proliferation.
    Anticancer Res. 2007 Nov-Dec;27(6A):3743-7 PMID: 17970037
  86. Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor.
    Cancer Res. 2006 Aug 15;66(16):7843-8 PMID: 16912155
  87. Safety, pharmacokinetics, immunogenicity, and biodistribution of (186)Re-labeled humanized monoclonal antibody BIWA 4 (Bivatuzumab) in patients with early-stage breast cancer.
    Cancer Biother Radiopharm. 2004 Dec;19(6):720-9 PMID: 15665619
  88. Chemokine receptor expression and function in childhood acute lymphoblastic leukemia of B-lineage.
    Leuk Res. 2006 Apr;30(4):365-72 PMID: 16118018
  89. Phase I trial with the CD44v6-targeting immunoconjugate bivatuzumab mertansine in head and neck squamous cell carcinoma.
    Oral Oncol. 2008 Sep;44(9):823-9 PMID: 18203652
  90. Prostate cancer stem cells: a new target for therapy.
    J Clin Oncol. 2008 Jun 10;26(17):2862-70 PMID: 18539965
  91. Targeting the Hedgehog pathway in cancer.
    Nat Rev Drug Discov. 2006 Dec;5(12):1026-33 PMID: 17139287
  92. In vitro and in vivo pharmacology and pharmacokinetics of a human engineered monoclonal antibody to epithelial cell adhesion molecule.
    Neoplasia. 2003 Mar-Apr;5(2):146-54 PMID: 12659687
  93. Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy.
    J Clin Oncol. 2008 Jun 10;26(17):2813-20 PMID: 18539959
  94. Inhibition of interleukin-6 with CNTO328, an anti-interleukin-6 monoclonal antibody, inhibits conversion of androgen-dependent prostate cancer to an androgen-independent phenotype in orchiectomized mice.
    Cancer Res. 2006 Mar 15;66(6):3087-95 PMID: 16540658
  95. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.
    Nature. 2003 May 15;423(6937):302-5 PMID: 12714971
  96. Dual inhibition of ErbB1 (EGFR/HER1) and ErbB2 (HER2/neu).
    Eur J Cancer. 2007 Feb;43(3):481-9 PMID: 17208435
  97. Recent advances in cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers.
    J Cell Mol Med. 2007 Sep-Oct;11(5):981-1011 PMID: 17979879
  98. Evaluation of soluble adhesion molecules CD44 (CD44st, CD44v5, CD44v6), ICAM-1, and VCAM-1 as tumor markers in head and neck cancer.
    Am J Otolaryngol. 2005 Sep-Oct;26(5):308-13 PMID: 16137528
  99. Exploiting tumour hypoxia in cancer treatment.
    Nat Rev Cancer. 2004 Jun;4(6):437-47 PMID: 15170446
  100. Trastuzumab--mechanism of action and use in clinical practice.
    N Engl J Med. 2007 Jul 5;357(1):39-51 PMID: 17611206
  101. Epithelial-mesenchymal transitions in tumour progression.
    Nat Rev Cancer. 2002 Jun;2(6):442-54 PMID: 12189386
  102. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer.
    Cell Stem Cell. 2007 Sep 13;1(3):313-23 PMID: 18371365
  103. Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis.
    Nature. 2006 Dec 21;444(7122):1083-7 PMID: 17183323
  104. Cancer stem cells, CD200 and immunoevasion.
    Trends Immunol. 2008 Oct;29(10):464-8 PMID: 18775673
  105. The tetraspanin CD9 modulates epidermal growth factor receptor signaling in cancer cells.
    J Cell Physiol. 2008 Jul;216(1):135-43 PMID: 18247373
  106. Tumor antigen targets and tumor immunotherapy.
    Front Biosci. 2006 Jan 01;11:337-43 PMID: 16146735
  107. Human colon cancer stem cells: a new paradigm in gastrointestinal oncology.
    J Clin Oncol. 2008 Jun 10;26(17):2828-38 PMID: 18539961
  108. CD24 is a new oncogene, early at the multistep process of colorectal cancer carcinogenesis.
    Gastroenterology. 2006 Aug;131(2):630-9 PMID: 16890615
  109. Mechanisms of killing by anti-CD20 monoclonal antibodies.
    Mol Immunol. 2007 Sep;44(16):3823-37 PMID: 17768100
  110. Targeted antiangiogenic therapy for cancer using Vitaxin: a humanized monoclonal antibody to the integrin alphavbeta3.
    Clin Cancer Res. 2000 Aug;6(8):3056-61 PMID: 10955784
  111. Hyaluronan-induced masking of ErbB2 and CD44-enhanced trastuzumab internalisation in trastuzumab resistant breast cancer.
    Eur J Cancer. 2007 Nov;43(16):2423-33 PMID: 17911008
  112. Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers.
    Br J Cancer. 2006 Jan 16;94(1):128-35 PMID: 16404366
  113. Production of functional chimaeric mouse/human antibody.
    Nature. 1984 Dec 13-19;312(5995):643-6 PMID: 6095115
  114. A monoclonal antibody against Wnt-1 induces apoptosis in human cancer cells.
    Neoplasia. 2004 Jan-Feb;6(1):7-14 PMID: 15068666
  115. Mechanisms of regulation of CXCR4/SDF-1 (CXCL12)-dependent migration and homing in multiple myeloma.
    Blood. 2007 Apr 1;109(7):2708-17 PMID: 17119115
  116. Inhibitory effects of anti-CXCR4 antibodies on human colon cancer cells.
    Cancer Immunol Immunother. 2005 Aug;54(8):781-91 PMID: 15592929
  117. Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy.
    Breast Cancer Res. 2008;10(2):R25 PMID: 18366788
  118. CD44-epidermal growth factor receptor interaction mediates hyaluronic acid-promoted cell motility by activating protein kinase C signaling involving Akt, Rac1, Phox, reactive oxygen species, focal adhesion kinase, and MMP-2.
    J Biol Chem. 2008 Aug 15;283(33):22513-28 PMID: 18577517
  119. Modulation of antibody pharmacokinetics by chemical polysialylation.
    Bioconjug Chem. 2008 Mar;19(3):643-50 PMID: 18307285
  120. The role of Notch in tumorigenesis: oncogene or tumour suppressor?
    Nat Rev Cancer. 2003 Oct;3(10):756-67 PMID: 14570040
  121. Combination therapy with fludarabine and rituximab followed by alemtuzumab in the first-line treatment of patients with chronic lymphocytic leukemia or small lymphocytic lymphoma: a phase 2 trial of the Minnie Pearl Cancer Research Network.
    Cancer. 2008 Mar 15;112(6):1288-95 PMID: 18189296
  122. Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics.
    Breast Cancer Res. 2008;10(1):R10 PMID: 18241344
  123. Targeting CD24 for treatment of colorectal and pancreatic cancer by monoclonal antibodies or small interfering RNA.
    Cancer Res. 2008 Apr 15;68(8):2803-12 PMID: 18413748
  124. Melanoma stem cells: the dark seed of melanoma.
    J Clin Oncol. 2008 Jun 10;26(17):2890-4 PMID: 18539969
  125. The hallmarks of cancer.
    Cell. 2000 Jan 7;100(1):57-70 PMID: 10647931
  126. Advances in cancer therapy with radiolabeled monoclonal antibodies.
    Q J Nucl Med Mol Imaging. 2006 Dec;50(4):248-64 PMID: 17043623
  127. Liver cancer stem cells.
    J Clin Oncol. 2008 Jun 10;26(17):2800-5 PMID: 18539957
  128. Increased beta1 integrin is associated with decreased survival in invasive breast cancer.
    Cancer Res. 2007 Jan 15;67(2):659-64 PMID: 17234776
  129. Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling.
    Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2445-50 PMID: 18263735
  130. The sonic hedgehog signaling network in development and neoplasia.
    Adv Anat Pathol. 2007 Sep;14(5):344-52 PMID: 17717435
  131. The unique physiology of solid tumors: opportunities (and problems) for cancer therapy.
    Cancer Res. 1998 Apr 1;58(7):1408-16 PMID: 9537241
  132. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice.
    Nature. 2007 Jan 4;445(7123):106-10 PMID: 17122772
  133. Effect of pegylation on pharmaceuticals.
    Nat Rev Drug Discov. 2003 Mar;2(3):214-21 PMID: 12612647
  134. ATP-binding-cassette transporters in hematopoietic stem cells and their utility as therapeutical targets in acute and chronic myeloid leukemia.
    Leukemia. 2007 Oct;21(10):2094-102 PMID: 17657220
  135. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma.
    Mol Cancer. 2006 Dec 02;5:67 PMID: 17140455
  136. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells.
    Nature. 2006 May 25;441(7092):475-82 PMID: 16598206
  137. Mining the Wnt pathway for cancer therapeutics.
    Nat Rev Drug Discov. 2006 Dec;5(12):997-1014 PMID: 17139285
  138. Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibody.
    Cancer Res. 1994 Mar 15;54(6):1561-5 PMID: 7511044
  139. Safety, biodistribution, pharmacokinetics, and immunogenicity of 99mTc-labeled humanized monoclonal antibody BIWA 4 (bivatuzumab) in patients with squamous cell carcinoma of the head and neck.
    Cancer Immunol Immunother. 2003 Sep;52(9):576-82 PMID: 14627130
  140. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma.
    Cancer Res. 2004 Oct 1;64(19):7011-21 PMID: 15466194
  141. A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia.
    Blood. 2001 Aug 15;98(4):1166-73 PMID: 11493466
  142. beta1-integrin-mediated signaling essentially contributes to cell survival after radiation-induced genotoxic injury.
    Oncogene. 2006 Mar 2;25(9):1378-90 PMID: 16247454
  143. Rituximab therapy in malignant lymphoma.
    Oncogene. 2007 May 28;26(25):3603-13 PMID: 17530014
  144. Skeletal localization and neutralization of the SDF-1(CXCL12)/CXCR4 axis blocks prostate cancer metastasis and growth in osseous sites in vivo.
    J Bone Miner Res. 2005 Feb;20(2):318-29 PMID: 15647826
  145. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway.
    Oncogene. 2008 Mar 13;27(12):1749-58 PMID: 17891174
  146. Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer.
    Oncogene. 2000 Mar 2;19(10):1288-96 PMID: 10713670
  147. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood.
    J Exp Med. 1997 Jan 6;185(1):111-20 PMID: 8996247
  148. Involvement of chemokine receptors in breast cancer metastasis.
    Nature. 2001 Mar 1;410(6824):50-6 PMID: 11242036
  149. Adhesion molecules and chemokines: the navigation system for circulating tumor (stem) cells to metastasize in an organ-specific manner.
    Clin Exp Metastasis. 2008;25(1):11-32 PMID: 17828597
  150. Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study.
    Blood. 2001 Dec 1;98(12):3212-20 PMID: 11719356
  151. HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion.
    Oncogene. 2008 Oct 16;27(47):6120-30 PMID: 18591932
  152. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells.
    Nature. 2005 Jun 16;435(7044):959-63 PMID: 15959515
  153. Identification of pancreatic cancer stem cells.
    Cancer Res. 2007 Feb 1;67(3):1030-7 PMID: 17283135
  154. The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells.
    J Mol Med (Berl). 2008 Sep;86(9):1025-32 PMID: 18535813
  155. Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy.
    PLoS One. 2008 Jun 18;3(6):e2428 PMID: 18560594
  156. Notch signaling as a therapeutic target in cancer: a new approach to the development of cell fate modifying agents.
    Oncogene. 2003 Sep 29;22(42):6598-608 PMID: 14528285
  157. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer.
    Nat Rev Drug Discov. 2004 May;3(5):391-400 PMID: 15136787
  158. CD133: molecule of the moment.
    J Pathol. 2008 Jan;214(1):3-9 PMID: 18067118
  159. Anticancer therapies combining antiangiogenic and tumor cell cytotoxic effects reduce the tumor stem-like cell fraction in glioma xenograft tumors.
    Cancer Res. 2007 Apr 15;67(8):3560-4 PMID: 17440065
  160. Hyaluronan and the interaction between CD44 and epidermal growth factor receptor in oncogenic signaling and chemotherapy resistance in head and neck cancer.
    Arch Otolaryngol Head Neck Surg. 2006 Jul;132(7):771-8 PMID: 16847188
  161. Prevalence of CD44+/CD24-/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis.
    Clin Cancer Res. 2005 Feb 1;11(3):1154-9 PMID: 15709183
  162. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4.
    Cell Stem Cell. 2007 Oct 11;1(4):389-402 PMID: 18371377
  163. Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer.
    Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1735-40 PMID: 9465086
  164. Identification of human aldehyde dehydrogenase 1 family member A1 as a novel CD8+ T-cell-defined tumor antigen in squamous cell carcinoma of the head and neck.
    Cancer Res. 2007 Nov 1;67(21):10538-45 PMID: 17974998
  165. The biology of the 17-1A antigen (Ep-CAM).
    J Mol Med (Berl). 1999 Oct;77(10):699-712 PMID: 10606205
  166. CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers.
    Br J Cancer. 2008 Jul 8;99(1):100-9 PMID: 18542072
  167. CD44: a new means to inhibit acute myeloid leukemia cell proliferation via p27Kip1.
    Blood. 2004 Feb 1;103(3):1059-68 PMID: 14525786
  168. In vitro and in vivo activity of MT201, a fully human monoclonal antibody for pancarcinoma treatment.
    Int J Cancer. 2002 Jul 1;100(1):101-10 PMID: 12115595
  169. Rational targeting of Notch signaling in cancer.
    Oncogene. 2008 Sep 1;27(38):5124-31 PMID: 18758481
Article Info
Journal
mAbs
Abbr.
MAbs
ISSN
1942-0870
DOI
10.4161/mabs.1.1.7347
Email
m.deonarain@imperial.ac.uk
Published
2009-00-00
Pages
12-25
Language
English
Region
United States
NLM ID
101479829
PMCID
PMC2715180
Subset
IM
Grants
Wellcome Trust · United Kingdom
Cancer Research UK · United Kingdom
External Links
PubMed source DOI: 10.4161/mabs.1.1.7347 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2