Skip to main content
Erschienen in: Cancer and Metastasis Reviews 1/2020

09.01.2020

Drug repurposing towards targeting cancer stem cells in pediatric brain tumors

verfasst von: Hisham F. Bahmad, Mohamad K. Elajami, Talal El Zarif, Jolie Bou-Gharios, Tamara Abou-Antoun, Wassim Abou-Kheir

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 1/2020

Einloggen, um Zugang zu erhalten

Abstract

In the pediatric population, brain tumors represent the most commonly diagnosed solid neoplasms and the leading cause of cancer-related deaths globally. They include low-grade gliomas (LGGs), medulloblastomas (MBs), and other embryonal, ependymal, and neuroectodermal tumors. The mainstay of treatment for most brain tumors includes surgical intervention, radiation therapy, and chemotherapy. However, resistance to conventional therapy is widespread, which contributes to the high mortality rates reported and lack of improvement in patient survival despite advancement in therapeutic research. This has been attributed to the presence of a subpopulation of cells, known as cancer stem cells (CSCs), which reside within the tumor bulk and maintain self-renewal and recurrence potential of the tumor. An emerging promising approach that enables identifying novel therapeutic strategies to target CSCs and overcome therapy resistance is drug repurposing or repositioning. This is based on using previously approved drugs with known pharmacokinetic and pharmacodynamic characteristics for indications other than their traditional ones, like cancer. In this review, we provide a synopsis of the drug repurposing methodologies that have been used in pediatric brain tumors, and we argue how this selective compilation of approaches, with a focus on CSC targeting, could elevate drug repurposing to the next level.
Literatur
12.
Zurück zum Zitat Bahmad, H. F., & Poppiti, R. J. (submitted). Medulloblastoma cancer stem cells: molecular signatures and therapeutic targets. Journal of Clinical Pathology. Bahmad, H. F., & Poppiti, R. J. (submitted). Medulloblastoma cancer stem cells: molecular signatures and therapeutic targets. Journal of Clinical Pathology.
27.
Zurück zum Zitat Xu, H. S., Qin, X. L., Zong, H. L., He, X. G., & Cao, L. (2017). Cancer stem cell markers in glioblastoma—an update. European Review for Medical and Pharmacological Sciences, 21(14), 3207–3211.PubMed Xu, H. S., Qin, X. L., Zong, H. L., He, X. G., & Cao, L. (2017). Cancer stem cell markers in glioblastoma—an update. European Review for Medical and Pharmacological Sciences, 21(14), 3207–3211.PubMed
36.
Zurück zum Zitat Handley, M. V. (2015). GSK-3 inhibitors in glioblastoma therapy: mechanisms of action. BOSTON UNIVERSITY. Handley, M. V. (2015). GSK-3 inhibitors in glioblastoma therapy: mechanisms of action. BOSTON UNIVERSITY.
38.
Zurück zum Zitat Chirasani, S. R., Leukel, P., Gottfried, E., Hochrein, J., Stadler, K., Neumann, B., et al. (2013). Diclofenac inhibits lactate formation and efficiently counteracts local immune suppression in a murine glioma model. International Journal of Cancer, 132(4), 843–853. https://doi.org/10.1002/ijc.27712.CrossRefPubMed Chirasani, S. R., Leukel, P., Gottfried, E., Hochrein, J., Stadler, K., Neumann, B., et al. (2013). Diclofenac inhibits lactate formation and efficiently counteracts local immune suppression in a murine glioma model. International Journal of Cancer, 132(4), 843–853. https://​doi.​org/​10.​1002/​ijc.​27712.CrossRefPubMed
40.
47.
Zurück zum Zitat Rasmussen, E. R., Pottegard, A., Bygum, A., von Buchwald, C., Homoe, P., & Hallas, J. (2019). Angiotensin II receptor blockers are safe in patients with prior angioedema related to angiotensin-converting enzyme inhibitors - a nationwide registry-based cohort study. Journal of Internal Medicine, 285(5), 553–561. https://doi.org/10.1111/joim.12867.CrossRefPubMed Rasmussen, E. R., Pottegard, A., Bygum, A., von Buchwald, C., Homoe, P., & Hallas, J. (2019). Angiotensin II receptor blockers are safe in patients with prior angioedema related to angiotensin-converting enzyme inhibitors - a nationwide registry-based cohort study. Journal of Internal Medicine, 285(5), 553–561. https://​doi.​org/​10.​1111/​joim.​12867.CrossRefPubMed
50.
Zurück zum Zitat Arrieta, O., Villarreal-Garza, C., Vizcaino, G., Pineda, B., Hernandez-Pedro, N., Guevara-Salazar, P., et al. (2015). Association between AT1 and AT2 angiotensin II receptor expression with cell proliferation and angiogenesis in operable breast cancer. Tumour Biology, 36(7), 5627–5634. https://doi.org/10.1007/s13277-015-3235-3.CrossRefPubMed Arrieta, O., Villarreal-Garza, C., Vizcaino, G., Pineda, B., Hernandez-Pedro, N., Guevara-Salazar, P., et al. (2015). Association between AT1 and AT2 angiotensin II receptor expression with cell proliferation and angiogenesis in operable breast cancer. Tumour Biology, 36(7), 5627–5634. https://​doi.​org/​10.​1007/​s13277-015-3235-3.CrossRefPubMed
51.
54.
Zurück zum Zitat Nakada M., M. T, Pyko I., Hayashi Y. and Hamada J. (2011). The pivotal roles of GSK3β in glioma biology In M. Garami (Ed.), Molecular Targets of CNS Tumors IntechOpen. Nakada M., M. T, Pyko I., Hayashi Y. and Hamada J. (2011). The pivotal roles of GSK3β in glioma biology In M. Garami (Ed.), Molecular Targets of CNS Tumors IntechOpen.
62.
Zurück zum Zitat Chalhoub, R. M., Bahmad, H. F., Harati, H., Assi, S., Araji, T., Bou-Gharios, J., et al. (2019). Specific inhibition of GSK-3β by Tideglusib: potential therapeutic target for neuroblastoma cancer stem cells. Submitted. Chalhoub, R. M., Bahmad, H. F., Harati, H., Assi, S., Araji, T., Bou-Gharios, J., et al. (2019). Specific inhibition of GSK-3β by Tideglusib: potential therapeutic target for neuroblastoma cancer stem cells. Submitted.
68.
Zurück zum Zitat Yalon, M., Rood, B., MacDonald, T. J., McCowage, G., Kane, R., Constantini, S., et al. (2013). A feasibility and efficacy study of rapamycin and erlotinib for recurrent pediatric low-grade glioma (LGG). Pediatric Blood & Cancer, 60(1), 71–76. https://doi.org/10.1002/pbc.24142.CrossRef Yalon, M., Rood, B., MacDonald, T. J., McCowage, G., Kane, R., Constantini, S., et al. (2013). A feasibility and efficacy study of rapamycin and erlotinib for recurrent pediatric low-grade glioma (LGG). Pediatric Blood & Cancer, 60(1), 71–76. https://​doi.​org/​10.​1002/​pbc.​24142.CrossRef
83.
87.
Zurück zum Zitat Sheikholeslami, K., Ali Sher, A., Lockman, S., Kroft, D., Ganjibakhsh, M., Nejati-Koshki, K., et al. (2019). Simvastatin induces apoptosis in medulloblastoma brain tumor cells via mevalonate cascade prenylation substrates. Cancers (Basel), 11(7). https://doi.org/10.3390/cancers11070994. Sheikholeslami, K., Ali Sher, A., Lockman, S., Kroft, D., Ganjibakhsh, M., Nejati-Koshki, K., et al. (2019). Simvastatin induces apoptosis in medulloblastoma brain tumor cells via mevalonate cascade prenylation substrates. Cancers (Basel), 11(7). https://​doi.​org/​10.​3390/​cancers11070994.
98.
Zurück zum Zitat Yamada, M., Ikeuchi, T., & Hatanaka, H. (1997). The neurotrophic action and signalling of epidermal growth factor. Progress in Neurobiology, 51(1), 19–37.CrossRefPubMed Yamada, M., Ikeuchi, T., & Hatanaka, H. (1997). The neurotrophic action and signalling of epidermal growth factor. Progress in Neurobiology, 51(1), 19–37.CrossRefPubMed
100.
Zurück zum Zitat Gilbertson, R. J., Perry, R. H., Kelly, P. J., Pearson, A. D., & Lunec, J. (1997). Prognostic significance of HER2 and HER4 coexpression in childhood medulloblastoma. Cancer Research, 57(15), 3272–3280.PubMed Gilbertson, R. J., Perry, R. H., Kelly, P. J., Pearson, A. D., & Lunec, J. (1997). Prognostic significance of HER2 and HER4 coexpression in childhood medulloblastoma. Cancer Research, 57(15), 3272–3280.PubMed
102.
Zurück zum Zitat Bal, M. M., Das Radotra, B., Srinivasan, R., & Sharma, S. C. (2006). Does c-erbB-2 expression have a role in medulloblastoma prognosis? Indian Journal of Pathology & Microbiology, 49(4), 535–539. Bal, M. M., Das Radotra, B., Srinivasan, R., & Sharma, S. C. (2006). Does c-erbB-2 expression have a role in medulloblastoma prognosis? Indian Journal of Pathology & Microbiology, 49(4), 535–539.
106.
Zurück zum Zitat Chan, K. K., Oza, A. M., & Siu, L. L. (2003). The statins as anticancer agents. Clinical Cancer Research, 9(1), 10–19.PubMed Chan, K. K., Oza, A. M., & Siu, L. L. (2003). The statins as anticancer agents. Clinical Cancer Research, 9(1), 10–19.PubMed
108.
112.
Zurück zum Zitat Guerini, A. E., Triggiani, L., Maddalo, M., Bonu, M. L., Frassine, F., Baiguini, A., et al. (2019). Mebendazole as a candidate for drug repurposing in oncology: an extensive review of current literature. Cancers (Basel), 11(9). https://doi.org/10.3390/cancers11091284. Guerini, A. E., Triggiani, L., Maddalo, M., Bonu, M. L., Frassine, F., Baiguini, A., et al. (2019). Mebendazole as a candidate for drug repurposing in oncology: an extensive review of current literature. Cancers (Basel), 11(9). https://​doi.​org/​10.​3390/​cancers11091284.
122.
Zurück zum Zitat Witzig, T. E., Timm, M., Stenson, M., Svingen, P. A., & Kaufmann, S. H. (2000). Induction of apoptosis in malignant B cells by phenylbutyrate or phenylacetate in combination with chemotherapeutic agents. Clinical Cancer Research, 6(2), 681–692.PubMed Witzig, T. E., Timm, M., Stenson, M., Svingen, P. A., & Kaufmann, S. H. (2000). Induction of apoptosis in malignant B cells by phenylbutyrate or phenylacetate in combination with chemotherapeutic agents. Clinical Cancer Research, 6(2), 681–692.PubMed
124.
129.
Zurück zum Zitat Yao, J. C., Wang, L., Wei, D., Gong, W., Hassan, M., Wu, T. T., et al. (2004). Association between expression of transcription factor Sp1 and increased vascular endothelial growth factor expression, advanced stage, and poor survival in patients with resected gastric cancer. Clinical Cancer Research, 10(12 Pt 1), 4109–4117. https://doi.org/10.1158/1078-0432.ccr-03-0628.CrossRefPubMed Yao, J. C., Wang, L., Wei, D., Gong, W., Hassan, M., Wu, T. T., et al. (2004). Association between expression of transcription factor Sp1 and increased vascular endothelial growth factor expression, advanced stage, and poor survival in patients with resected gastric cancer. Clinical Cancer Research, 10(12 Pt 1), 4109–4117. https://​doi.​org/​10.​1158/​1078-0432.​ccr-03-0628.CrossRefPubMed
134.
Zurück zum Zitat Lopez-Barcons, L., Maurer, B. J., Kang, M. H., & Reynolds, C. P. (2017). P450 inhibitor ketoconazole increased the intratumor drug levels and antitumor activity of fenretinide in human neuroblastoma xenograft models. International Journal of Cancer, 141(2), 405–413. https://doi.org/10.1002/ijc.30706.CrossRefPubMed Lopez-Barcons, L., Maurer, B. J., Kang, M. H., & Reynolds, C. P. (2017). P450 inhibitor ketoconazole increased the intratumor drug levels and antitumor activity of fenretinide in human neuroblastoma xenograft models. International Journal of Cancer, 141(2), 405–413. https://​doi.​org/​10.​1002/​ijc.​30706.CrossRefPubMed
139.
Zurück zum Zitat Saulnier Sholler, G. L., Kalkunte, S., Greenlaw, C., McCarten, K., & Forman, E. (2006). Antitumor activity of Nifurtimox observed in a patient with neuroblastoma. Journal of Pediatric Hematology/Oncology, 28(10). Saulnier Sholler, G. L., Kalkunte, S., Greenlaw, C., McCarten, K., & Forman, E. (2006). Antitumor activity of Nifurtimox observed in a patient with neuroblastoma. Journal of Pediatric Hematology/Oncology, 28(10).
150.
Zurück zum Zitat Nishio, N., Fujita, M., Tanaka, Y., Maki, H., Zhang, R., Hirosawa, T., et al. (2012). Zoledronate sensitizes neuroblastoma-derived tumor-initiating cells to cytolysis mediated by human γδ T cells. Journal of Immunotherapy, 35(8). Nishio, N., Fujita, M., Tanaka, Y., Maki, H., Zhang, R., Hirosawa, T., et al. (2012). Zoledronate sensitizes neuroblastoma-derived tumor-initiating cells to cytolysis mediated by human γδ T cells. Journal of Immunotherapy, 35(8).
157.
Zurück zum Zitat Binlateh, T., Tanasawet, S., Rattanaporn, O., Sukketsiri, W., & Hutamekalin, P. (2019). Metformin promotes neuronal differentiation via crosstalk between Cdk5 and Sox6 in neuroblastoma cells. Evidence-based complementary and alternative medicine : eCAM, 2019, 1765182–1765182. https://doi.org/10.1155/2019/1765182.CrossRef Binlateh, T., Tanasawet, S., Rattanaporn, O., Sukketsiri, W., & Hutamekalin, P. (2019). Metformin promotes neuronal differentiation via crosstalk between Cdk5 and Sox6 in neuroblastoma cells. Evidence-based complementary and alternative medicine : eCAM, 2019, 1765182–1765182. https://​doi.​org/​10.​1155/​2019/​1765182.CrossRef
162.
Zurück zum Zitat Shah, R. D., Jagtap, J. C., Mruthyunjaya, S., Shelke, G. V., Pujari, R., Das, G., et al. (2013). Sodium valproate potentiates staurosporine-induced apoptosis in neuroblastoma cells via Akt/survivin independently of HDAC inhibition. Journal of Cellular Biochemistry, 114(4), 854–863. https://doi.org/10.1002/jcb.24422.CrossRefPubMed Shah, R. D., Jagtap, J. C., Mruthyunjaya, S., Shelke, G. V., Pujari, R., Das, G., et al. (2013). Sodium valproate potentiates staurosporine-induced apoptosis in neuroblastoma cells via Akt/survivin independently of HDAC inhibition. Journal of Cellular Biochemistry, 114(4), 854–863. https://​doi.​org/​10.​1002/​jcb.​24422.CrossRefPubMed
163.
Zurück zum Zitat Groh, T., Hrabeta, J., Ashraf Khalil, M., Doktorova, H., Eckschlager, T., & Stiborova, M. (2015). The synergistic effects of DNA-damaging drugs cisplatin and etoposide with a histone deacetylase inhibitor valproate in high-risk neuroblastoma cells. International Journal of Oncology, 47(1), 343–352.CrossRefPubMed Groh, T., Hrabeta, J., Ashraf Khalil, M., Doktorova, H., Eckschlager, T., & Stiborova, M. (2015). The synergistic effects of DNA-damaging drugs cisplatin and etoposide with a histone deacetylase inhibitor valproate in high-risk neuroblastoma cells. International Journal of Oncology, 47(1), 343–352.CrossRefPubMed
165.
166.
167.
Zurück zum Zitat Zheng, X., Naiditch, J., Czurylo, M., Jie, C., Lautz, T., Clark, S., et al. (2013). Differential effect of long-term drug selection with doxorubicin and vorinostat on neuroblastoma cells with cancer stem cell characteristics. Cell Death & Disease, 4(7), e740–e740. https://doi.org/10.1038/cddis.2013.264.CrossRef Zheng, X., Naiditch, J., Czurylo, M., Jie, C., Lautz, T., Clark, S., et al. (2013). Differential effect of long-term drug selection with doxorubicin and vorinostat on neuroblastoma cells with cancer stem cell characteristics. Cell Death & Disease, 4(7), e740–e740. https://​doi.​org/​10.​1038/​cddis.​2013.​264.CrossRef
168.
169.
Zurück zum Zitat Bahmad, H. F., Mouhieddine, T. H., Chalhoub, R. M., Assi, S., Araji, T., Chamaa, F., et al. (2018). The Akt/mTOR pathway in cancer stem/progenitor cells is a potential therapeutic target for glioblastoma and neuroblastoma. Oncotarget, 9(71), 33549-33561, https://doi.org/10.18632/oncotarget.26088. Bahmad, H. F., Mouhieddine, T. H., Chalhoub, R. M., Assi, S., Araji, T., Chamaa, F., et al. (2018). The Akt/mTOR pathway in cancer stem/progenitor cells is a potential therapeutic target for glioblastoma and neuroblastoma. Oncotarget, 9(71), 33549-33561, https://​doi.​org/​10.​18632/​oncotarget.​26088.
170.
Zurück zum Zitat Cerna, T., Hrabeta, J., Eckschlager, T., Frei, E., Schmeiser, H. H., Arlt, V. M., et al. (2018). The histone deacetylase inhibitor valproic acid exerts a synergistic cytotoxicity with the DNA-damaging drug Ellipticine in neuroblastoma cells. International Journal of Molecular Sciences, 19(1), 164. https://doi.org/10.3390/ijms19010164.CrossRefPubMedCentral Cerna, T., Hrabeta, J., Eckschlager, T., Frei, E., Schmeiser, H. H., Arlt, V. M., et al. (2018). The histone deacetylase inhibitor valproic acid exerts a synergistic cytotoxicity with the DNA-damaging drug Ellipticine in neuroblastoma cells. International Journal of Molecular Sciences, 19(1), 164. https://​doi.​org/​10.​3390/​ijms19010164.CrossRefPubMedCentral
171.
Zurück zum Zitat Chen, Y. U. N., Tsai, Y.-H., & Tseng, S.-H. (2011). Combined Valproic acid and celecoxib treatment induced synergistic cytotoxicity and apoptosis in neuroblastoma cells. Anticancer Research, 31(6), 2231–2239.PubMed Chen, Y. U. N., Tsai, Y.-H., & Tseng, S.-H. (2011). Combined Valproic acid and celecoxib treatment induced synergistic cytotoxicity and apoptosis in neuroblastoma cells. Anticancer Research, 31(6), 2231–2239.PubMed
Metadaten
Titel
Drug repurposing towards targeting cancer stem cells in pediatric brain tumors
verfasst von
Hisham F. Bahmad
Mohamad K. Elajami
Talal El Zarif
Jolie Bou-Gharios
Tamara Abou-Antoun
Wassim Abou-Kheir
Publikationsdatum
09.01.2020
Verlag
Springer US
Erschienen in
Cancer and Metastasis Reviews / Ausgabe 1/2020
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-019-09840-2

Weitere Artikel der Ausgabe 1/2020

Cancer and Metastasis Reviews 1/2020 Zur Ausgabe

EditorialNotes

Preface

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.