New promising drug targets in cancer- and mtastasis-initiating cells

Drug Discovery Today

Volumn 15, Issue 9-10, 2010, Pages 354-364

  Mimeault, Murielle ^a,b   Batra, Surinder K ^a,b  

^a UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

^b UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; ALPHA INTERFERON; ANTIMETASTATIC AGENT; ANTINEOPLASTIC AGENT; BEVACIZUMAB; CD133 MONOCLONAL ANTIBODY; CYCLOPAMINE; CYCLOPHOSPHAMIDE; DOFEQUIDAR; DOXORUBICIN; ERLOTINIB; FLUOROURACIL; GEFITINIB; GEMCITABINE; IPI 269609; LAPATINIB; MITOXANTRONE; MONOCLONAL ANTIBODY; OLIGOSACCHARIDE; PERIFOSINE; RAPAMYCIN; SARIDEGIB; SMALL INTERFERING RNA; SULFORAPHANE; TRANSCRIPTION FACTOR NANOG; TRANSCRIPTION FACTOR SOX2; TRASTUZUMAB; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; UNCLASSIFIED DRUG; UNINDEXED DRUG; VERAPAMIL; NEW DRUG;

BREAST CANCER; CANCER GROWTH; CANCER RADIOTHERAPY; CANCER RESISTANCE; CANCER STEM CELL; CANCER SURVIVAL; DNA REPAIR; DRUG EFFICACY; EPITHELIAL MESENCHYMAL TRANSITION; GLIOMA; HUMAN; MELANOMA; METASTASIS; METASTASIS INHIBITION; MOLECULARLY TARGETED THERAPY; NONHUMAN; PANCREAS CANCER; REVIEW; SIGNAL TRANSDUCTION; SPINAL CORD GLIOMA; TUMOR MICROENVIRONMENT; ANIMAL; BIOLOGICAL MODEL; DRUG DELIVERY SYSTEM; DRUG EFFECT; DRUG RESISTANCE; DRUG SCREENING; METHODOLOGY;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG DELIVERY SYSTEMS; DRUG RESISTANCE, NEOPLASM; DRUG SCREENING ASSAYS, ANTITUMOR; DRUGS, INVESTIGATIONAL; HUMANS; MODELS, BIOLOGICAL; NEOPLASM METASTASIS; SIGNAL TRANSDUCTION;

EID: 77950853025     PISSN: 13596446     EISSN: 18785832     Source Type: Journal    
DOI: 10.1016/j.drudis.2010.03.009     Document Type: Review

References (168)

1. Schrama, D. et al. (2006) Antibody targeted drugs as cancer therapeutics. Nat. Rev. Drug Discov. 5, 147-159
2. Gray-Schopfer, V. et al. (2007) Melanoma biology and new targeted therapy. Nature 445, 851-857
3. Sorscher, S.M. (2007) Biological therapy update in colorectal cancer. Expert Opin. Biol. Ther. 7, 509-519
4. Mimeault, M. et al. (2008) Recent advances on the molecular mechanisms involved in the drug resistance of cancer cells and novel targeting therapies. Clin. Pharmacol. Ther. 83, 673-691 (Pubitemid 351559599)
5. Sathornsumetee, S. et al. (2007) Molecularly targeted therapy for malignant glioma. Cancer 110, 13-24
6. Le Tourneau, C. et al. (2008) New developments in multitargeted therapy for patients with solid tumours. Cancer Treat. Rev. 34, 37-48 (Pubitemid 351168610)
7. Rosa, D.D. et al. (2008) Molecular-targeted therapies: lessons from years of clinical development. Cancer Treat. Rev. 34, 61-80 (Pubitemid 351168606)
8. Spangenberg, H.C. et al. (2009) Targeted therapy for hepatocellular carcinoma. Nat. Rev. Gastroenterol. Hepatol. 6, 423-432
9. Jemal, A. et al. (2008) Cancer statistics, 2008. CA Cancer J. Clin. 58, 71-96 (Pubitemid 351521864)
10. Mimeault, M. and Batra, S.K. (2010) New advances on<- critical implications of tumor- and metastasis-initiating cells in cancer progression, treatment resistance and disease recurrence. Histol. Histopathol. 25.
11. Mimeault, M. and Batra, S.K. (2010) Novel therapies against aggressive and recurrent epithelial cancers by molecular targeting tumor- and metastasisinitiating cells and their progenies. Anticancer Agents Med. Chem. 10, 137-151 Special issue
12. Vaish, M. (2007) Mismatch repair deficiencies transforming stem cells into cancer stem cells and therapeutic implications. Mol. Cancer 6, 26
13. Rizo, A. et al. (2006) Signaling pathways in self-renewing hematopoietic and leukemic stem cells: do all stem cells need a niche? Hum. Mol. Genet. 15, R210-R219 (Pubitemid 44446796)
14. Kim, C.F. et al. (2005) Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121, 823-835 (Pubitemid 40806415)
15. Mimeault, M. et al. (2007) Recent advances on cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers. J. Mol. Cell. Med. 11, 981-1011 (Pubitemid 350037046)
16. Ginestier, C. et al. (2007) ALDHl is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1, 555-567 (Pubitemid 350056407)
17. Matsui, W. et al. (2008) Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res. 68, 190-197 (Pubitemid 351380120)
18. Mimeault, M. and Batra, S.K. (2008) Recent progress on tissue-resident adult stem cell biology and their therapeutic implications. Stem Cell Rev. 4, 27-49
19. Mimeault, M. and Batra, S.K. (2008) Recent progress on normal and malignant pancreatic stem/progenitor cell research: therapeutic implications for the treatment of type 1 or 2 diabetes mellitus and aggressive pancreatic cancer. Gut57, 1456-1468
20. Mimeault, M. et al. (2008) Functions of normal and malignant prostatic stem/ progenitor cells in tissue regeneration and cancer progression and novel targeting therapies. Endocr. Rev. 29, 234-252 (Pubitemid 351519692)
21. Chiba, T. (2007) Enhanced self-renewal capability in hepatic stem/progenitor cells drives cancer initiation. Gastroenterology 133, 937-950
22. Chen, B.Y. et al. (2007) Hedgehog is involved in prostate basal cell hyperplasia formation and its progressing towards tumorigenesis. Biochem. Biophys. Res. Commun. 357, 1084-1089
23. Liu, S. et al. (2006) Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 66, 6063-6071
24. Korkaya, H. et al. (2008) HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene 27, 6120-6130
25. Mimeault, M. and Batra, S.K. (2009) Aging of tissue-resident adult stem/progenitor cells and their pathological consequences. Panminerva Med. 51, 57-79
26. Mimeault, M. and Batra, S.K. (2009) Recent insights into the molecular mechanisms involved in aging and the malignant transformation of adult stem/progenitor cells and their therapeutic implications. Ageing Res. Rev. 8, 94-112
27. Mimeault, M. and Batra, S.K. (2008) Targeting of cancer stem/progenitor cells plus stem cell-based therapies: the ultimate hope for treating and curing aggressive and recurrent cancers. Panminerva Med. 50, 3-18
28. Mimeault, M. and Batra, S.K. (2010) Recent advances on skin-resident stem/ progenitor cell functions in skin regeneration, aging and cancers and novel antiaging and cancer therapies. J. Cell. Mol. Med. 14, 116-134
29. Alcantara, L.S. et al. (2009) Malignant astrocytomas originate from neural stem/ progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell 15,45-56
30. Zhu, Y. et al. (2005) Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. Cancer Cell 8, 119-130 (Pubitemid 41132741)
31. Galli, R. et al. (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res. 64, 7011-7021 (Pubitemid 39331011)
32. Singh, S.K. (2004) Identification of human brain tumour initiating cells. Nature 432, 396-401
33. Al-Hajj, M. et al. (2003) Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sei. U.S.A. 100, 3983-3988 (Pubitemid 36418143)
34. Eramo, A. et al. (2008) Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ. 15, 504-514 (Pubitemid 351267301)
35. Yang, Z.F. et al. (2008) Significance of CD90(+) cancer stem cells in human liver cancer. Cancer Cell 13, 153-166 (Pubitemid 351163165)
36. Hermann, P.C. et al. (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1, 313-323 (Pubitemid 47355323)
37. Zhang, S. et al. (2008) Identification and characterization of ovarian cancerinitiating cells from primary human tumors. Cancer Res. 68, 4311-4320
38. Liu, G. et al. (2006) Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol. Cancer 5, 67
39. Schatton, T. et al. (2008) Identification of cells initiating human melanomas. Nature 451, 345-349
40. Maitland, NJ. et al. (2006) Prostate cancer stem cells: a target for new therapies. Ermt. Schering. Found. Symp. Proc. 5, 155-179
41. Ricci-Vitiani, L. et al. (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445, 111-115 (Pubitemid 46067311)
42. Alvero, A.B. et al. (2009) Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance. Cell Cycle 8, 158-166
43. Baba, T. et al. (2009) Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells. Oncogene 28, 209-218
44. Haraguchi, N. et al. (2006) Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells 24, 506-513 (Pubitemid 44464754)
45. Hirschmann-Jax, C. et al. (2004) A distinct "side population" of cells with high drug efflux capacity in human tumor cells. Proc. Natl. Acad. Sei. U.S.A. 101,14228-14233 (Pubitemid 39305058)
46. Levina, V. et al. (2008) Drug-selected human lung cancer stem cells: cytokine network, tumorigenic and metastatic properties. PLoS One 3, e3077
47. Klarmann, G.J. et al. (2009) Invasive prostate cancer cells are tumor initiating cells that have a stem cell-like genomic signature. Clin. Exp. Metastasis 26, 433-446
48. Hope, K.J. et al. (2004) Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat. Immunol. 5, 738-743 (Pubitemid 39023306)
49. Fang, D. et al. (2005) A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res. 65, 9328-9337 (Pubitemid 41508000)
50. Wright, M.H. et al. (2008) Brcal breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics. Breast Cancer Res. 10, R10
51. Shi, G.M. et al. (2008) Identification of side population cells in human hepatocellular carcinoma cell lines with stepwise metastatic potentials. J. Cancer Res. Clin. Oncol. 134, 1155-1163
52. Huang, D. et al. (2009) Isolation and identification of cancer stem-like cells in esophageal carcinoma cell lines. Stem Cells Dev. 18, 465-473
53. Huang, Q. et al. (2008) Glioma stem cells are more aggressive in recurrent tumors with malignant progression than in the primary tumor, and both can be maintained long-term in vitro. BMC Cancer 8, 304
54. Todaro, M. et al. (2007) Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell 1, 389-402 (Pubitemid 47506537)
55. Wang, J. et al. (2007) Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. Cancer Res. 67, 3716-3724 (Pubitemid 46762157)
56. Brabletz, T. et al. (2005) Opinion: migrating cancer stem cells-an integrated concept of malignant tumour progression. Nat. Rev. Cancer 5, 744-749 (Pubitemid 41486367)
57. Tso, C.L. et al. (2006) Primary glioblastomas express mesenchymal stem-like properties. Mol. Cancer Res. 4, 607-619
58. Mimeault, M. and Batra, S.K. (2007) Interplay of distinct growth factors during epithelial-mesenchymal transition of cancer progenitor cells and molecular targeting as novel cancer therapies. Ann. Oncol. 18, 1605-1619 (Pubitemid 47506246)
59. Mimeault, M. and Batra, S.K. (2007) Functions of tumorigenic and migrating cancer progenitor cells in cancer progression and metastasis and their therapeutic implications. Cancer Metastasis Rev. 26, 203-214 (Pubitemid 46452192)
60. Mani, S.A. et al. (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133, 704-715 (Pubitemid 351636299)
61. Spaderna, S. (2007) Epithelial-mesenchymal and mesenchymal-epithelial transitions during cancer progression. Verh. Dtsch. Ges. Pathol. 91, 21-28
62. Storci, G. et al. (2008) The basal-like breast carcinoma phenotype is regulated by SLUG gene expression. J. Pathol. 214, 25-37
63. Shah, A.N. et al. (2007) Development and characterization of gemcitabineresistant pancreatic tumor cells. Ann. Surg. Oncol. 14, 3629-3637 (Pubitemid 350160137)
64. Morel, A.P. et al. (2008) Generation of breast cancer stem cells through epithelialmesenchymal transition. PLoS One 3, e2888
65. Balic, M. et al. (2006) Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin. Cancer Res. 12, 5615-5621 (Pubitemid 44629587)
66. Aktas, B. et al. (2009) Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res. 11, R46
67. Theodoropoulos, P.A. et al. (2010) Circulating tumor cells with a putative stem cell phenotype in peripheral blood of patients with breast cancer. Cancer Lett. 288, 99-106
68. Fillmore, CM. and Kuperwasser, C. (2008) Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res. 10, R25
69. Li, X. et al. (2008) Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J. Natl. Cancer Inst. 100, 672-679
70. Jimeno, A. et al. (2009) A direct pancreatic cancer xenograft model as a platform for cancer stem cell therapeutic development. Mol. Cancer Ther. 8, 310-314
71. Hong, S.P. et al. (2009) CD44-positive cells are responsible for gemcitabine resistance in pancreatic cancer cells. Int. J. Cancer 125, 2323-2331
72. Wang, Y.H. et al. (2009) A side population of cells from a human pancreatic carcinoma cell line harbors cancer stem cell characteristics. Neoplasma 56,371-378
73. Kennedy, J.A. et al. (2007) Comment on "Tumor growth need not be driven by rare cancer stem cells". Science 318, 1722
74. Quintana, E. et al. (2008) Efficient tumour formation by single human melanoma cells. Nature 456, 593-598
75. Bao, S. et al. (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444, 756-760 (Pubitemid 44949604)
76. Das, B. et al. (2008) Hypoxia enhances tumor sternness by increasing the invasive and tumorigenic side population fraction. Stem Cells 26, 1818-1830
77. Shmelkov, S.V. et al. (2008) CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors. J. Clin. Invest. 118, 2111-2120 (Pubitemid 351872330)
78. Dylla, S.J. et al. (2008) Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS One 3, e2428
79. Schmidt, C et al. (2008) Lapatinib study supports cancer stem cell hypothesis, encourages industry research. J. Natl. Cancer Inst. 100, 694-695
80. Griffera, F. et al. (2009) Different response of human glioma tumor-initiating cells to EGFR kinase inhibitors. J. Biol. Chem. 284, 7138-7148
81. Gupta, P.B. et al. (2009) Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138, 645-659
82. Kelly, P.N. et al. (2007) Tumor growth need not be driven by rare cancer stem cells. Science 317, 337 (Pubitemid 47106366)
83. Ponti, D. et al. (2005) Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 65, 5506-5511 (Pubitemid 40911148)
84. Yang, Z.F. et al. (2008) Identification of local and circulating cancer stem cells in human liver cancer. Hepatology 47, 919-928
85. Morimoto, K. et al. (2009) Stem cell marker aldehyde dehydrogenase 1-positive breast cancers are characterized by negative estrogen receptor, positive human epidermal growth factor receptor type 2, and high Ki67 expression. Cancer Sci. 100, 1062-1068
86. Loebinger, M.R. et al. (2008) Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade. Br. J. Cancer 98, 380-387 (Pubitemid 351161265)
87. Zhou, J. et al. (2008) NF-kappaB pathway inhibitors preferentially inhibit breast cancer stem-like cells. Breast Cancer Res. Treat. 111, 419-427
88. Zhou, J. et al. (2007) Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc. Natl. Acad. Sei. U.S.A. 104, 16158-16163 (Pubitemid 350099378)
89. Phillips, T.M. et al. (2006) The response of CD24(-/low)/CD44+ breast cancerinitiating cells to radiation. J. Natl. Cancer Inst. 98, 1777-1785 (Pubitemid 46017929)
90. Ma, S. et al. (2008) CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene 27, 1749-1758 (Pubitemid 351380265)
91. Schatton, T. et al. (2010) Modulation of T-cell activation by malignant melanoma initiating cells. Cancer Res. 70, 697-708
92. Dean, M. et al. (2005) Tumour stem cells and drug resistance. Nat. Rev. Cancer 5, 275-284 (Pubitemid 40488633)
93. Zhang, X. et al. (2008) Treatment of radioresistant stem-like esophageal cancer cells by an apoptotic gene-armed, telomerase-specific oncolytic adenovirus. Clin. Cancer Res. 14, 2813-2823
94. Shervington, A. and Lu, C (2008) Expression of multidrug resistance genes in normal and cancer stem cells. Cancer Invest. 26, 535-542 (Pubitemid 351892589)
95. Frank, N.Y. et al. (2005) ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. Cancer Res. 65, 4320-4333 (Pubitemid 40775671)
96. Hadnagy, A. et al. (2006) SP analysis may be used to identify cancer stem cell populations. Exp. Cell Res. 312, 3701-3710
97. Mimeault, M. et al. (2010) Cytotoxic effects induced by docetaxel, gefitinib and cyclopamine on side population and non-side population cell fractions from human tumorigenic and invasive prostate cancer cells. Mol. Cancer Ther. 9, 617-630
98. Sung, J.M. et al. (2008) Characterization of a stem cell population in lung cancer A549 cells. Stochern. Blophys. Res. Commun. 371, 163-167
99. Ho, M.M. et al. (2007) Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res. 67, 4827-4833 (Pubitemid 46910191)
100. Tanaka, H. et al. (2009) The Hedgehog signaling pathway plays an essential role in maintaining the CD44+ CD24-/low subpopulation and the side population of breast cancer cells. Anticancer Res. 29, 2147-2157
101. Mimeault, M. and Batra, S.K. (2009) Characterization of non-malignant and malignant prostatic stem/progenitor cells by Hoecsht side population method. Methods Mol. Biol. 568, 139-149
102. Katayama, R. et al. (2009) Dofequidar fumarate sensitizes cancer stem-like side population cells to chemotherapeutic drugs by inhibiting ABCG2/BCRP-mediated drug export. Cancer Set. 100, 2060-2068
103. Huang, M. et al. (2010) Whole genome expression profiling reveals a significant role for the cell Junction and apoptosis pathways in breast cancer stem cells. Mol. Biotechnol.
104. Zhou, J. et al. (2007) Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc. Natl. Acad. Sci. U. S. A. 104, 16158-16163 (Pubitemid 350099378)
105. Christgen, M. et al. (2007) Identification of a distinct side population of cancer cells in the Cal-51 human breast carcinoma cell line. Mol. Cell. Biochem. 306, 201-212 (Pubitemid 350001832)
106. Xu, J.X. et al. (2007) High tolerance to apoptotic stimuli induced by serum depletion and ceramide in side-population cells: high expression of CD55 as a novel character for side-population. Exp. Cell Res. 313, 1877-1885
107. Kondo, T. et al. (2004) Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc. Natl. Acad. Sci. U.S.A. 101, 781-786 (Pubitemid 38121035)
108. Chen, J.S. et al. (2006) EGFR regulates the side population in head and neck squamous cell carcinoma. Laryngoscope 116, 401-406 (Pubitemid 44318100)
109. Mitsutake, N. et al. (2007) Characterization of side population in thyroid cancer cell lines: cancer stem-like cells are enriched partly but not exclusively. Endocrinology 148, 1797-1803 (Pubitemid 46457095)
110. Dey, D. et al. (2009) Phenotypic and functional characterization of human mammary stem/progenitor cells in long term culture. PLoS One 4, e5329
111. Feldmann, G. et al. (2007) Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. Cancer Res. 67, 2187-2196 (Pubitemid 46424238)
112. Bar, E.E. et al. (2007) Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma. Stem Cells 25, 2524-2533 (Pubitemid 47582744)
113. Tanei, T. et al. (2009) Association of breast cancer stem cells identifiedby aldehyde dehydrogenase 1 expression with resistance to sequential Paclitaxel and epirubicin-based chemotherapy for breast cancers. Clin. Cancer Res. 15, 4234-4241
114. Charafe-Jauffret, E. et al. (2010) Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer. Clin. Cancer Res. 16, 45-55
115. Duester, G. et al. (2003) Cytosolic retinoid dehydrogenases govern ubiquitous metabolism of retinol to retinaldehyde followed by tissue-specific metabolism to retinoic acid. Chem. Biol. Interact. 143-144, 201-210 (Pubitemid 36246442)
116. Chute, J.P. et al. (2006) Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells. Proc. Natl. Acad. Sci. U.S.A. 103, 11707-11712 (Pubitemid 44182515)
117. Wagner, E. et al. (2006) Retinoic acid delineates the topography of neuronal plasticity in postnatal cerebral cortex. Eur. J. Neurosci. 24, 329-340 (Pubitemid 44100325)
118. Marchitti, S.A. et al. (2008) Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily. Expert Opin. Drug Metab. Toxicol. 4, 697-720 (Pubitemid 352003194)
119. Rice, K. L. et al. (2008) Overexpression of stem cell associated ALDH1A1, a target of the leukemogenic transcription factor TLX1/HOX11, inhibits lymphopoiesis and promotes myelopoiesis in murine hematopoietic progenitors. Leuk. Res. 32, 873-883
120. Ginestier, C et al. (2009) Retinoid signaling regulates breast cancer stem cell differentiation. Cell Cycle 8, 3297-3302
121. Walsh, N. et al. (2008) Aldehyde dehydrogenase 1A1 and gelsolin identified as novel invasion-modulating factors in conditioned medium of pancreatic cancer cells. J. Proteomics 71, 561-571
122. Widschwendter, M. et al. (2000) Methylation and silencing of the retinoic acid receptor-beta2 gene in breast cancer. J. Natl. Cancer Inst. 92, 826-832 (Pubitemid 30368039)
123. Rexer, B.N. et al. (2001) Retinoic acid biosynthesis by normal human breast epithelium is via aldehyde dehydrogenase 6, absent in MCF-7 cells. Cancer Res. 61, 7065-7070 (Pubitemid 32951773)
124. Moreb, J.S. et al. (2005) Retinoic acid down-regulates aldehyde dehydrogenase and increases cytotoxicity of 4-hydroperoxycyclophosphamide and acetaldehyde. J. Pharmacol. Exp. Ther. 312, 339-345 (Pubitemid 40096487)
125. Elizondo, G. et al. (2009) Retinoic acid modulates retinaldehyde dehydrogenase 1 gene expression through the induction of GADD153-C/EBPbeta interaction. Stochern. Pharmacol. 77, 248-257
126. Epping, M.T. et al. (2005) The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell 122, 835-847 (Pubitemid 41345202)
127. Kurrey, N.K. et al. (2009) Snail and slug mediate radio- and chemo-resistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Stem Cells 27, 2059-2068
128. Rappa, G. et al. (2008) The stem cell-associated antigen CD133 (Prominin-1) is a molecular therapeutic target for metastatic melanoma. Stem Cells 26, 3008-3017
129. Gilg, A.G. et al. (2008) Targeting hyaluronan interactions in malignant gliomas and their drug-resistant multipotent progenitors. Clin. Cancer Res. 14, 1804-1813 (Pubitemid 351469467)
130. Karhadkar, S.S. et al. (2004) Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature 431, 707-712 (Pubitemid 39382619)
131. Tanaka, H. et al. (2009) The Hedgehog signaling pathway plays an essential role in maintaining the CD44+ CD24-/low subpopulation and the side population of breast cancer cells. Anticancer Res 29, 2147-2157
132. Marian, C.O. et al. (2010) The telomerase antagonist, imetelstat, efficiently targets glioblastoma tumor-initiating cells leading to decreased proliferation and tumor growth. Clin. Cancer Res. 16, 154-163
133. Ginestier, C et al. (2010) CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J. Clin. Invest. 120, 485-497
134. Magnifico, A. et al. (2009) Tumor-initiating cells of HER2-positive carcinoma cell lines express the highest oncoprotein levels and are sensitive to trastuzumab. Clin. Cancer Res. 15, 2010-2021
135. Clement, V. et al. (2007) HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr. Biol. 17, 165-172 (Pubitemid 46107823)
136. Feldmann, G. et al. (2008) An orally bioavailable small-molecule inhibitor of Hedgehog signaling inhibits tumor initiation and metastasis in pancreatic cancer. Mol. Cancer Ther. 7, 2725-2735
137. Xu, Q. et al. (2008) Hedgehog signaling regulates brain tumor-initiating cell proliferation and portends shorter survival for patients with PTEN-coexpressing glioblastomas. Stem Cells 26, 3018-3026
138. Mimeault, M. et al. (2007) Improvement of cytotoxic effects of mitoxantrone on hormone-refractory metastatic prostate cancer cells by co-targeting epidermal growth factor receptor and hedgehog signaling cascades. Growth Factors 25,400-416 (Pubitemid 351455006)
139. Olive, K.P. et al. (2009) Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 324, 1457-1461
140. Miki, J. et al. (2007) Identification of putative stem cell markers, CD133 and CXCR4, in hTERT-immortalized primary nonmalignant and malignant tumorderived human prostate epithelial cell lines and in prostate cancer specimens. Cancer Res. 67, 3153-3161 (Pubitemid 46724852)
141. Hu, C et al. (2008) Analysis of ABCG2 expression and side population identifies intrinsic drug efflux in the HCC cell line MHCC-97L and its modulation by Akt signaling. Carcinogenesis 29, 2289-2297
142. Johannessen, T.C. et al. (2009) Highly infiltrative brain tumours show reduced chemosensitivity associated with a stem cell-like phenotype. Neuropathol. Appl. Neurobiol. 35, 380-393
143. Kallifatidis, G. et al. (2009) Sulforaphane targets pancreatic tumour-initiating cells by NF-kappaB-induced antiapoptotic signalling. Gut 58, 949-963
144. Korkaya, H. et al. (2009) Regulation of mammary stem/progenitor cells by PTEN/ Akt/beta-catenin signaling. PLoS Biol. 7, el000121
145. Schatzlein, A.G. et al. (2006) Delivering cancer stem cell therapies-a role for nanomedicines? Eur. J. Cancer 42, 1309-1315 (Pubitemid 44208866)
146. Mine, T. et al. (2009) Breast cancer cells expressing stem cell markers CD44+ CD24 Io are eliminated by Numb-1 peptide-activated T cells. Cancer Immunol. Immunother. 58, 1185-1194
147. Bansal, T. et al. (2009) Novel formulation approaches for optimizing delivery of anticancer drugs based on P-glycoprotein modulation. Drug Discov. Today
148. Nandi, S. et al. (2008) Low-dose radiation enhances survivin-mediated virotherapy against malignant glioma stem cells. Cancer Res. 68, 5778-5784
149. Eriksson, M. (2007) Oncolytic adenoviruses kill breast cancer initiating CD44+ CD24-/10W cells. Mol. Ther. 15, 2088-2093
150. Cripe, T.P. et al. (2009) Targeting cancer-initiating cells with oncolytic viruses. Mol. Ther. 17, 1677-1682
151. Esau, C.C. and Monia, B.P. (2007) Therapeutic potential for microRNAs. Adv. Drug Deliv. Rev. 59, 101-114 (Pubitemid 46773050)
152. Silber, J. et al. (2008) miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Med. 6, 14
153. Ji, Q. et al. (2008) Restoration of tumor suppressor miR-34 inhibits human p53mutant gastric cancer tumorspheres. BMC Cancer 8, 266
154. Ji, Q. et al. (2009) MicroRNA miR-34 inhibits human pancreatic cancer tumorinitiating cells. PLoS One 4, e6816
155. Yu, F. et al. (2007) let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 131, 1109-1123 (Pubitemid 350235025)
156. Sell, S. et al. (2004) Stem cell origin of cancer and differentiation therapy. Crlt. Rev. Oncol. Hematol. 51, 1-28 (Pubitemid 38781748)
157. Moserle, L. et al. (2008) The side population of ovarian cancer cells is a primary target of IFN-alpha antitumor effects. Cancer Res. 68, 5658-5668
158. Petrie, K. et al. (2009) Differentiation therapy of acute myeloid leukemia: past, present and future. Curr. Opin. Hematol. 16, 84-91
159. Folkins, C et al. (2007) Anticancer therapies combining antiangiogenic and tumor cell cytotoxic effects reduce the tumor stem-like cell fraction in glioma xenograft tumors. Cancer Res. 67, 3560-3564 (Pubitemid 46762138)
160. Calabrese, C et al. (2007) A perivascular niche for brain tumor stem cells. Cancer Cell 11, 69-82 (Pubitemid 46054518)
161. Borovski, T. et al. (2009) Tumor microvasculature supports proliferation and expansion of glioma-propagating cells. Int. J. Cancer 125, 1222-1230
162. Rafii, S. et al. (2002) Vascular and haematopoietic stem cells: novel targets for antiangiogenesis therapy? Nat. Rev. Cancer 2, 826-835 (Pubitemid 37328901)
163. Davidoff, A.M. et al. (2001) Bone marrow-derived cells contribute to tumor neovasculature and, when modified to express an angiogenesis inhibitor, can restrict tumor growth in mice. Clin. Cancer Res. 7, 2870-2879 (Pubitemid 32911397)
164. Loebinger, M.R. et al. (2009) Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer. Cancer Res. 69, 4134-4142
165. Theunissen, J.W. and de Sauvage, F.J. (2009) Paracrine Hedgehog signaling in cancer. Cancer Res. 69, 6007-6010
166. Shaw, A. et al. (2009) The Sonic Hedgehog pathway stimulates prostate tumor growth by paracrine signaling and recapitulates embryonic gene expression in tumor myofibroblasts. Oncogene 28, 4480-4490
167. Kasper, M. et al. (2009) Hedgehog signalling in breast cancer. Carcinogenesis 30, 903-911
168. Nakamura, K. et al. (2010) Hedgehog promotes neovascularization in pancreatic cancers by regulating Ang-1 and IGF-I expression in bone-marrow derived proangiogenic cells. PLoS One 5, e8824