Stem Cell Reviews and Reports

, Volume 11, Issue 6, pp 909–918 | Cite as

Novel Small Molecule Inhibitors of Cancer Stem Cell Signaling Pathways

  • Danysh Abetov
  • Zhanar Mustapova
  • Timur Saliev
  • Denis Bulanin
  • Kanat Batyrbekov
  • Charles P. Gilman


The main aim of oncologists worldwide is to understand and then intervene in the primary tumor initiation and propagation mechanisms. This is essential to allow targeted elimination of cancer cells without altering normal mitotic cells. Currently, there are two main rival theories describing the process of tumorigenesis. According to the Stochastic Model, potentially any cell, once defunct, is capable of initiating carcinogenesis. Alternatively the Cancer Stem Cell (CSC) Model posits that only a small fraction of undifferentiated tumor cells are capable of triggering carcinogenesis. Like healthy stem cells, CSCs are also characterized by a capacity for self-renewal and the ability to generate differentiated progeny, possibly mediating treatment resistance, thus leading to tumor recurrence and metastasis. Moreover, molecular signaling profiles are similar between CSCs and normal stem cells, including Wnt, Notch and Hedgehog pathways. Therefore, development of novel chemotherapeutic agents and proteins (e.g., enzymes and antibodies) specifically targeting CSCs are attractive pharmaceutical candidates. This article describes small molecule inhibitors of stem cell pathways Wnt, Notch and Hedgehog, and their recent chemotherapy clinical trials.


Cancer Stem cells Inhibitor Wnt Notch Hedgehog Signaling pathway 



Authors are thankful for financial support provided through the grant “Analysis of gene expression for different stages of colorectal cancer” (‘Programme-targeted funding 2014–2017’; Government of Republic of Kazakhstan).

Author Contributions

All authors equally contributed to the design, literature analysis and writing of the manuscript.

Disclosure of Interest

The authors have no commercial, proprietary, or financial interest in the products or companies described in this article.


  1. 1.
    Reya, T., Morrison, S. J., Clarke, M. F., & Weissman, I. L. (2001). Stem cells, cancer, and cancer stem cells. Nature, 414, 105–11.CrossRefPubMedGoogle Scholar
  2. 2.
    Shackleton, M., Quintana, E., Fearon, E. R., & Morrison, S. J. (2009). Heterogeneity in cancer: cancer stem cells versus clonal evolution. Cell, 138, 822–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Dick, J. E. (2008). Stem cell concepts renew cancer research. Blood, 112, 4793–807.CrossRefPubMedGoogle Scholar
  4. 4.
    Iyer, K. S., & Saksena, V. N. (1970). A stochastic model for the growth of cells in cancer. Biometrics, 26, 401–10.CrossRefPubMedGoogle Scholar
  5. 5.
    Odoux, C., Fohrer, H., Hoppo, T., et al. (2008). A stochastic model for cancer stem cell origin in metastatic colon cancer. Cancer Research, 68, 6932–41.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Lapidot, T., Sirard, C., Vormoor, J., et al. (1994). A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature, 367, 645–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Bonnet, D., & Dick, J. E. (1997). Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Medicine, 3, 730–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Al-Hajj, M., & Clarke, M. F. (2004). Self-renewal and solid tumor stem cells. Oncogene, 23, 7274–82.CrossRefPubMedGoogle Scholar
  9. 9.
    Takebe, N., & Ivy, S. P. (2010). Controversies in cancer stem cells: targeting embryonic signaling pathways. Clinical Cancer Research, 16, 3106–12.CrossRefPubMedGoogle Scholar
  10. 10.
    Wang, W. K., Quan, Y., Fu, Q. B., et al. (2014). Dynamics between Cancer Cell Subpopulations Reveals a Model Coordinating with Both Hierarchical and Stochastic Concepts. PLoS One, 9, 1.Google Scholar
  11. 11.
    Takebe, N., Harris, P. J., Warren, R. Q., & Ivy, S. P. (2011). Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nature Reviews. Clinical Oncology, 8, 97–106.CrossRefPubMedGoogle Scholar
  12. 12.
    Klaus, A., & Birchmeier, W. (2008). Wnt signalling and its impact on development and cancer. Nature Reviews Cancer, 8, 387–98.CrossRefPubMedGoogle Scholar
  13. 13.
    Seifert, J. R. K., & Mlodzik, M. (2007). Frizzled/PCP signalling: a conserved mechanism regulating cell polarity and directed motility. Nature Reviews Genetics, 8, 126–38.CrossRefPubMedGoogle Scholar
  14. 14.
    Vermeulen, L., De Sousa, E. M. F., van der Heijden, M., et al. (2010). Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nature Cell Biology, 12, 468–76.CrossRefPubMedGoogle Scholar
  15. 15.
    Simon, M., Grandage, V. L., Linch, D. C., & Khwaja, A. (2005). Constitutive activation of the Wnt/beta-catenin signalling pathway in acute myeloid leukaemia. Oncogene, 24, 2410–20.CrossRefPubMedGoogle Scholar
  16. 16.
    Zhao, C., Blum, J., Chen, A., Kwon, H. Y., Jung, S. H., Cook, J. M., Lagoo, A., & Reya, T. (2007). Loss of beta-catenin impairs the renewal of normal and CML stem cells in vivo. Cancer Cell, 12, 528–41.PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Ooi, C. H., Ivanova, T., Wu, J., et al. (2009). Oncogenic pathway combinations predict clinical prognosis in gastric cancer. PLoS Genetics, 5, e1000676.PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    MacDonald, B. T., Tamai, K., & He, X. (2009). Wnt/beta-catenin signaling: components, mechanisms, and diseases. Developmental Cell, 17, 9–26.PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Takemaru, K. I., & Moon, R. T. (2000). The transcriptional coactivator CBP interacts with beta-catenin to activate gene expression. Journal of Cell Biology, 149, 249–54.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Hecht, A., Vleminckx, K., Stemmler, M. P., van Roy, F., & Kemler, R. (2000). The p300/CBP acetyltransferases function as transcriptional coactivators of beta-catenin in vertebrates. EMBO Journal, 19, 1839–50.PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    de Sousa, E. M. F., Vermeulen, L., Richel, D., & Medema, J. P. (2011). Targeting Wnt signaling in colon cancer stem cells. Clinical Cancer Research, 17, 647–53.CrossRefPubMedGoogle Scholar
  22. 22.
    Chen, B., Dodge, M. E., Tang, W., et al. (2009). Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nature Chemical Biology, 5, 100–7.PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Waaler, J., Machon, O., von Kries, J. P., et al. (2011). Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth. Cancer Research, 71, 197–205.CrossRefPubMedGoogle Scholar
  24. 24.
    Chen, Z., Venkatesan, A. M., Dehnhardt, C. M., et al. (2009). 2,4-Diamino-quinazolines as inhibitors of beta-catenin/Tcf-4 pathway: potential treatment for colorectal cancer. Bioorganic & Medicinal Chemistry Letters, 19, 4980–3.CrossRefGoogle Scholar
  25. 25.
    Trosset, J. Y., Dalvit, C., Knapp, S., et al. (2006). Inhibition of protein-protein interactions: the discovery of druglike beta-catenin inhibitors by combining virtual and biophysical screening. Proteins, 64, 60–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Huang, S. M., Mishina, Y. M., Liu, S., et al. (2009). Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature, 461, 614–20.CrossRefPubMedGoogle Scholar
  27. 27.
    Emami, K. H., Nguyen, C., Ma, H., et al. (2004). A small molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected]. Proceedings of the National Academy of Sciences of the United States of America, 101, 12682–7.PubMedCentralCrossRefPubMedGoogle Scholar
  28. 28.
    Shan, J., Shi, D. L., Wang, J., & Zheng, J. (2005). Identification of a specific inhibitor of the dishevelled PDZ domain. Biochemistry, 44, 15495–503.CrossRefPubMedGoogle Scholar
  29. 29.
    Takahashi-Yanaga, F., & Kahn, M. (2010). Targeting Wnt signaling: can we safely eradicate cancer stem cells? Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 16, 3153–62.CrossRefGoogle Scholar
  30. 30.
    Boon, E. M., Keller, J. J., Wormhoudt, T. A., Giardiello, F. M., Offerhaus, G. J., van der Neut, R., & Pals, S. T. (2004). Sulindac targets nuclear beta-catenin accumulation and Wnt signalling in adenomas of patients with familial adenomatous polyposis and in human colorectal cancer cell lines. British Journal of Cancer, 90, 224–9.PubMedCentralCrossRefPubMedGoogle Scholar
  31. 31.
    Ingham, P. W., & McMahon, A. P. (2001). Hedgehog signaling in animal development: paradigms and principles. Genes & Development, 15, 3059–87.CrossRefGoogle Scholar
  32. 32.
    Varjosalo, M., & Taipale, J. (2008). Hedgehog: functions and mechanisms. Genes & Development, 22, 2454–72.CrossRefGoogle Scholar
  33. 33.
    Amakye, D., Jagani, Z., & Dorsch, M. (2013). Unraveling the therapeutic potential of the Hedgehog pathway in cancer. Nature Medicine, 19, 1410–22.CrossRefPubMedGoogle Scholar
  34. 34.
    Taipale, J., Chen, J. K., Cooper, M. K., Wang, B., Mann, R. K., Milenkovic, L., Scott, M. P., & Beachy, P. A. (2000). Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine. Nature, 406, 1005–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Wu, J. Y., Xu, X. F., Xu, L., Niu, P. Q., Wang, F., Hu, G. Y., Wang, X. P., & Guo, C. Y. (2011). Cyclopamine blocked the growth of colorectal cancer SW116 cells by modulating some target genes of Gli1 in vitro. Hepato-Gastroenterology, 58, 1511–8.PubMedGoogle Scholar
  36. 36.
    LoRusso, P. M., Rudin, C. M., Borad, M. J., et al. (2008). A first-in-human, first-in-class, phase (ph) I study of systemic Hedgehog (Hh) pathway antagonist, GDC-0449, in patients (pts) with advanced solid tumors. Journal of Clinical Oncology, 26, 15.Google Scholar
  37. 37.
    Stein, A., & Bokemeyer, C. (2014). How to select the optimal treatment for first line metastatic colorectal cancer. World J Gastroenterol, 20(4), 899–907.Google Scholar
  38. 38.
    Lin, T. L., & Matsui, W. (2012). Hedgehog pathway as a drug target: smoothened inhibitors in development. OncoTargets and Therapy, 5, 47–58.Google Scholar
  39. 39.
    Jamieson, C., Cortes, J. E., Oehler, V., et al. (2011). Phase 1 dose-escalation study of PF-04449913, an oral hedgehog (Hh) inhibitor, in patients with select hematologic malignancies. Blood, 118, 195–6.Google Scholar
  40. 40.
    Artavanis-Tsakonas, S., Rand, M., & Lake, R. (1999). Notch signaling: cell fate control and signal integration in development. Science, 284, 770–6.Google Scholar
  41. 41.
    Reedijk, M., Odorcic, S., Zhang, H., et al. (2008). Activation of Notch signaling in human colon adenocarcinoma. International Journal of Oncology, 33, 1223–9.Google Scholar
  42. 42.
    Meng, R. D., Shelton, C. C., Li, Y. M., Qin, L. X., Notterman, D., Paty, P. B., & Schwartz, G. K. (2009). gamma-Secretase inhibitors abrogate oxaliplatin-induced activation of the Notch-1 signaling pathway in colon cancer cells resulting in enhanced chemosensitivity. Cancer Research, 69, 573–82.Google Scholar
  43. 43.
    Huynh, C., Poliseno, L., Segura, M. F., et al. (2011). The Novel Gamma Secretase Inhibitor RO4929097 Reduces the Tumor Initiating Potential of Melanoma. PLoS One, 6(9), e25264.Google Scholar
  44. 44.
    Deangelo, D. J., Stone, R. M., Silverman, L. B., et al. (2006). A phase I clinical trial of the notch inhibitor MK-0752 in patients with T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) and other leukemias. Journal of Clinical Oncology, 24, 357s-s.Google Scholar
  45. 45.
    Fouladi, M., Stewart, C. F., Olson, J., et al. (2011). Phase I trial of MK-0752 in children with refractory CNS malignancies: a pediatric brain tumor consortium study. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 29, 3529–34.CrossRefGoogle Scholar
  46. 46.
    Ridgway, J., Zhang, G., Wu, Y., et al. (2006). Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature, 444, 1083–7.CrossRefPubMedGoogle Scholar
  47. 47.
    Rudge, J. S., Thurston, G., Davis, S., Papadopoulos, N., Gale, N., Wiegand, S. J., & Yancopoulos, G. D. (2005). VEGF trap as a novel antiangiogenic treatment currently in clinical trials for cancer and eye diseases, and VelociGene- based discovery of the next generation of angiogenesis targets. Cold Spring Harbor Symposia on Quantitative Biology, 70, 411–8.CrossRefPubMedGoogle Scholar
  48. 48.
    Noguera-Troise, I., Daly, C., Papadopoulos, N. J., et al. (2006). Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature, 444, 1032–7.CrossRefPubMedGoogle Scholar
  49. 49.
    Fischer, M., Yen, W. C., Kapoun, A. M., Wang, M., O’Young, G., Lewicki, J., Gurney, A., & Hoey, T. (2011). Anti-DLL4 inhibits growth and reduces tumor-initiating cell frequency in colorectal tumors with oncogenic KRAS mutations. Cancer Research, 71, 1520–5.CrossRefPubMedGoogle Scholar
  50. 50.
    Visvader, J. E., & Lindeman, G. J. (2008). Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nature Reviews Cancer, 8, 755–68.CrossRefPubMedGoogle Scholar
  51. 51.
    Harbinski, F., Craig, V. J., Sanghavi, S., et al. (2012). Rescue screens with secreted proteins reveal compensatory potential of receptor tyrosine kinases in driving cancer growth. Cancer Discovery, 2, 948–59.CrossRefPubMedGoogle Scholar
  52. 52.
    Burrell, R. A., McGranahan, N., Bartek, J., & Swanton, C. (2013). The causes and consequences of genetic heterogeneity in cancer evolution. Nature, 501, 338–45.CrossRefPubMedGoogle Scholar
  53. 53.
    Lagasse, E. (2008). Cancer stem cells with genetic instability: the best vehicle with the best engine for cancer. Gene Therapy, 15, 136–42.CrossRefPubMedGoogle Scholar
  54. 54.
    Miura, M., Miura, Y., Padilla-Nash, H. M., et al. (2006). Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation. Stem Cells, 24, 1095–103.CrossRefPubMedGoogle Scholar
  55. 55.
    Shiras, A., Chettiar, S. T., Shepal, V., Rajendran, G., Prasad, G. R., & Shastry, P. (2007). Spontaneous transformation of human adult nontumorigenic stem cells to cancer stem cells is driven by genomic instability in a human model of glioblastoma. Stem Cells, 25, 1478–89.CrossRefPubMedGoogle Scholar
  56. 56.
    Lee, H. J., Wang, N. X., Shi, D. L., & Zheng, J. J. (2009). Sulindac inhibits canonical Wnt signaling by blocking the PDZ domain of the protein dishevelled. Angewandte Chemie-International Edition, 48, 6448–52.CrossRefGoogle Scholar
  57. 57.
    Taipale, J., Chen, J. K., Cooper, M. K., Wang, B. L., Mann, R. K., Milenkovic, L., Scott, M. P., & Beachy, P. A. (2000). Effects of oncogenic mutations in smoothened and patched can be reversed by cyclopamine. Nature, 406, 1005–9.CrossRefPubMedGoogle Scholar
  58. 58.
    Gajjar, A., Stewart, C. F., Ellison, D. W., et al. (2013). Phase I study of vismodegib in children with recurrent or refractory medulloblastoma: a pediatric brain tumor consortium study. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 19, 6305–12.CrossRefGoogle Scholar
  59. 59.
    LoRusso, P. (2009). Targeting the hedgehog pathway in medulloblastoma and advanced basal cell cancer therapy. Cancer Biology & Therapy, 8, v-vi.Google Scholar
  60. 60.
    Barginear, M., Clotfelter, A., & Van Poznak, C. (2009). Markers of bone metabolism in women receiving aromatase inhibitors for early-stage breast cancer. Clinical Breast Cancer, 9, 72–6.CrossRefPubMedGoogle Scholar
  61. 61.
    Jimeno, A., Weiss, G. J., Miller, W. H., et al. (2013). Phase I study of the hedgehog pathway inhibitor IPI-926 in adult patients with solid tumors. Clinical Cancer Research, 19, 2766–74.PubMedCentralCrossRefPubMedGoogle Scholar
  62. 62.
    Williams, J. A. (2003). Hedgehog signaling pathway as a target for therapeutic intervention in basal cell carcinoma. Drug News & Perspectives, 16, 657–62.CrossRefGoogle Scholar
  63. 63.
    Barginear, M. F., Leung, M., & Budman, D. R. (2009). The hedgehog pathway as a therapeutic target for treatment of breast cancer. Breast Cancer Research and Treatment, 116, 239–46.CrossRefPubMedGoogle Scholar
  64. 64.
    Rodon, J., Tawbi, H. A., Thomas, A. L., et al. (2014). A phase I, multicenter, open-label, first-in-human, dose-escalation study of the oral smoothened inhibitor Sonidegib (LDE225) in patients with advanced solid tumors. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 20, 1900–9.CrossRefGoogle Scholar
  65. 65.
    Schott, A. F., Landis, M. D., Dontu, G., et al. (2013). Preclinical and clinical studies of gamma secretase inhibitors with docetaxel on human breast tumors. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 19, 1512–24.CrossRefGoogle Scholar
  66. 66.
    LoConte, N. K., Razak, A. R., Ivy, P., et al. (2015). A multicenter phase 1 study of gamma -secretase inhibitor RO4929097 in combination with capecitabine in refractory solid tumors. Investigational New Drugs, 33, 169–76.CrossRefPubMedGoogle Scholar
  67. 67.
    Diaz-Padilla, I., Wilson, M. K., Clarke, B. A., et al. (2015). A phase II study of single-agent RO4929097, a gamma-secretase inhibitor of Notch signaling, in patients with recurrent platinum-resistant epithelial ovarian cancer: a study of the Princess Margaret, Chicago and California phase II consortia. Gynecologic oncology.Google Scholar
  68. 68.
    De Jesus-Acosta, A., Laheru, D., Maitra, A., et al. (2014). A phase II study of the gamma secretase inhibitor RO4929097 in patients with previously treated metastatic pancreatic adenocarcinoma. Investigational New Drugs, 32, 739–45.PubMedCentralCrossRefPubMedGoogle Scholar
  69. 69.
    Richter, S., Bedard, P. L., Chen, E. X., et al. (2014). A phase I study of the oral gamma secretase inhibitor R04929097 in combination with gemcitabine in patients with advanced solid tumors (PHL-078/CTEP 8575). Investigational New Drugs, 32, 243–9.PubMedCentralCrossRefPubMedGoogle Scholar
  70. 70.
    Tolcher, A. W., Messersmith, W. A., Mikulski, S. M., et al. (2012). Phase I study of RO4929097, a gamma secretase inhibitor of Notch signaling, in patients with refractory metastatic or locally advanced solid tumors. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 30, 2348–53.CrossRefGoogle Scholar
  71. 71.
    Sahebjam, S., Bedard, P. L., Castonguay, V., et al. (2013). A phase I study of the combination of ro4929097 and cediranib in patients with advanced solid tumours (PJC-004/NCI 8503). British Journal of Cancer, 109, 943–9.PubMedCentralCrossRefPubMedGoogle Scholar
  72. 72.
    Olsauskas-Kuprys, R., Zlobin, A., & Osipo, C. (2013). Gamma secretase inhibitors of Notch signaling. OncoTargets and Therapy, 6, 943–55.PubMedCentralPubMedGoogle Scholar
  73. 73.
    Egloff, A. M., & Grandis, J. R. (2012). Molecular pathways: context-dependent approaches to Notch targeting as cancer therapy. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 18, 5188–95.CrossRefGoogle Scholar
  74. 74.
    Tong, G., Wang, J. S., Sverdlov, O., et al. (2012). Multicenter, randomized, double-blind, placebo-controlled, single-ascending dose study of the oral gamma-secretase inhibitor BMS-708163 (Avagacestat): tolerability profile, pharmacokinetic parameters, and pharmacodynamic markers. Clinical Therapeutics, 34, 654–67.CrossRefPubMedGoogle Scholar
  75. 75.
    Gurney, A., Axelrod, F., Bond, C. J., et al. (2012). Wnt pathway inhibition via the targeting of Frizzled receptors results in decreased growth and tumorigenicity of human tumors. Proceedings of the National Academy of Sciences of the United States of America, 109, 11717–22.PubMedCentralCrossRefPubMedGoogle Scholar
  76. 76.
    Yabuuchi, S., Pai, S. G., Campbell, N. R., et al. (2013). Notch signaling pathway targeted therapy suppresses tumor progression and metastatic spread in pancreatic cancer. Cancer Letters, 335, 41–51.PubMedCentralCrossRefPubMedGoogle Scholar
  77. 77.
    Messersmith, W. A., Shapiro, G. I., Cleary, J. M., et al. (2015). A Phase I, dose-finding study in patients with advanced solid malignancies of the oral gamma-secretase inhibitor PF-03084014. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 21, 60–7.CrossRefGoogle Scholar
  78. 78.
    Smith, D. C., Eisenberg, P. D., Manikhas, G., et al. (2014). A phase I dose escalation and expansion study of the anticancer stem cell agent demcizumab (anti-DLL4) in patients with previously treated solid tumors. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 20, 6295–303.CrossRefGoogle Scholar
  79. 79.
    Zemskova, M., Wechter, W., Bashkirova, S., Chen, C. S., Reiter, R., & Lilly, M. B. (2006). Gene expression profiling in R-flurbiprofen-treated prostate cancer: R-Flurbiprofen regulates prostate stem cell antigen through activation of AKT kinase. Biochemical Pharmacology, 72, 1257–67.CrossRefPubMedGoogle Scholar
  80. 80.
    Le, P. N., McDermott, J. D., & Jimeno, A. (2015). Targeting the Wnt pathway in human cancers: therapeutic targeting with a focus on OMP-54 F28. Pharmacology & Therapeutics, 146, 1–11.CrossRefGoogle Scholar
  81. 81.
    Previs, R. A., Coleman, R. L., Harris, A. L., & Sood, A. K. (2015). Molecular pathways: translational and therapeutic implications of the notch signaling pathway in cancer. Clinical Cancer Research, 21, 955–61.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Danysh Abetov
    • 1
  • Zhanar Mustapova
    • 1
  • Timur Saliev
    • 1
  • Denis Bulanin
    • 2
  • Kanat Batyrbekov
    • 3
  • Charles P. Gilman
    • 4
  1. 1.Laboratory of Translational Medicine and Life Sciences Technologies, Centre for Life SciencesNazarbayev UniversityAstanaKazakhstan
  2. 2.School of MedicineNazarbayev UniversityAstanaKazakhstan
  3. 3.Research Institute of Traumatology and OrthopedicsAstanaKazakhstan
  4. 4.School of Science and TechnologyNazarbayev UniversityAstanaKazakhstan

Personalised recommendations