publication . Article . 2014

Targeting of the MYCN protein with small molecule c-MYC inhibitors.

Müller, Inga; Larsson, Karin; Frenzel, Anna; Oliynyk, Ganna; Zirath, Hanna; Prochownik, Edward V.; Westwood, Nicholas J.; Henriksson, Marie Arsenian;
Open Access English
  • Published: 01 May 2014 Journal: PLoS ONE, volume 9, issue 5 (issn: 1932-6203, eissn: 1932-6203, Copyright policy)
  • Publisher: Public Library of Science (PLoS)
Abstract
This study was funded by grants from the Swedish Research Council and the Swedish Cancer Society. IM and HZ were recipients of graduate student grants from KI (KID), MAH was recipient of a Senior Investigator Award from the Swedish Cancer Society, and NJW was a Royal Society University Research Fellow when this work began. Members of the MYC family are the most frequently deregulated oncogenes in human cancer and are often correlated with aggressive disease and/or poorly differentiated tumors. Since patients with MYCN-amplified neuroblastoma have a poor prognosis, targeting MYCN using small molecule inhibitors could represent a promising therapeutic approach....
Subjects
mesheuropmc: neoplasms
free text keywords: Cancer Treatment, Biotechnology, Cell Differentiation, Research Article, Molecular Cell Biology, Secondary structure analyses, MYC/MAX, Neurons, Oncology, Neuronal differentiation, Murine development, Neural-network, Clinical Medicine, Tumor dormancy, Proteins, Neoplastic phenotype, Pharmacology, Q Science, Circular-dichroism spectra, Cellular Types, Biology and Life Sciences, Pediatric Oncology, Developmental Biology, Animal Cells, Medicine, Basic Cancer Research, Drug Research and Development, Biomacromolecule-Ligand Interactions, Q, Induced apoptosis, R, Cell Biology, Biochemistry, Science, Medicine and Health Sciences, N-MYC, Small Molecules
54 references, page 1 of 4

1 Vita M, Henriksson M (2006) The Myc oncoprotein as a therapeutic target for human cancer. Semin Cancer Biol 16: 318–330.16934487 [PubMed]

2 Meyer N, Penn LZ (2008) Reflecting on 25 years with MYC. Nat Rev Cancer 8: 976–990.19029958 [PubMed]

3 Luscher B, Larsson LG (1999) The basic region/helix-loop-helix/leucine zipper domain of Myc proto-oncoproteins: function and regulation. Oncogene 18: 2955–2966.10378692 [PubMed]

4 Malynn BA, de Alboran IM, O'Hagan RC, Bronson R, Davidson L, et al (2000) N-myc can functionally replace c-myc in murine development, cellular growth and differentiation. Genes and Dev 14: 1390–1399.10837031 [OpenAIRE] [PubMed]

5 Downs KM, Martin GR, Bishop JM (1989) Contrasting patterns of myc and N-myc expression during gastrulation of the mouse embryo. Genes Dev 3: 860–869.2663644 [PubMed]

6 Zimmerman KA, Yancopoulos GD, Collum RG, Smith RK, Kohl NE, et al (1986) Differential expression of myc family genes during murine development. Nature 319: 780–783.2419762 [PubMed]

7 Hirvonen H, Makela TP, Sandberg M, Kalimo H, Vuorio E, et al (1990) Expression of the myc proto-oncogenes in developing human fetal brain. Oncogene 5: 1787–1797.2284098 [PubMed]

8 Mugrauer G, Alt FW, Ekblom P (1988) N-myc proto-oncogene expression during organogenesis in the developing mouse as revealed by in situ hybridization. J Cell Biol 107: 1325–1335.3049618 [OpenAIRE] [PubMed]

9 Stanton BR, Parada LF (1992) The N-myc proto-oncogene: developmental expression and in vivo site-directed mutagenesis. Brain Pathol 2: 71–83.1341949 [PubMed]

10 Albihn A, Johnsen JI, Henriksson MA (2010) MYC in oncogenesis and as a target for cancer therapies. Adv Cancer Res 107: 163–224.20399964 [PubMed]

11 Brodeur GM (2003) Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer 3: 203–216.12612655 [PubMed]

12 Maris JM, Hogarty MD, Bagatell R, Cohn SL (2007) Neuroblastoma. Lancet 369: 2106–2120.17586306 [PubMed]

13 Larsson LG, Henriksson MA (2010) The Yin and Yang f unctions of the Myc oncoprotein in cancer development and as targets for therapy. Exp Cell Res 316: 1429–1437.20382143 [PubMed]

14 Prochownik EV, Vogt PK (2010) Therapeutic Targeting of Myc. Genes Cancer 1: 650–659.21132100 [OpenAIRE] [PubMed]

15 Felsher DW (2010) MYC Inactivation Elicits Oncogene Addiction through Both Tumor Cell-Intrinsic and Host-Dependent Mechanisms. Genes Cancer 1: 597–604.21037952 [OpenAIRE] [PubMed]

54 references, page 1 of 4
Abstract
This study was funded by grants from the Swedish Research Council and the Swedish Cancer Society. IM and HZ were recipients of graduate student grants from KI (KID), MAH was recipient of a Senior Investigator Award from the Swedish Cancer Society, and NJW was a Royal Society University Research Fellow when this work began. Members of the MYC family are the most frequently deregulated oncogenes in human cancer and are often correlated with aggressive disease and/or poorly differentiated tumors. Since patients with MYCN-amplified neuroblastoma have a poor prognosis, targeting MYCN using small molecule inhibitors could represent a promising therapeutic approach....
Subjects
mesheuropmc: neoplasms
free text keywords: Cancer Treatment, Biotechnology, Cell Differentiation, Research Article, Molecular Cell Biology, Secondary structure analyses, MYC/MAX, Neurons, Oncology, Neuronal differentiation, Murine development, Neural-network, Clinical Medicine, Tumor dormancy, Proteins, Neoplastic phenotype, Pharmacology, Q Science, Circular-dichroism spectra, Cellular Types, Biology and Life Sciences, Pediatric Oncology, Developmental Biology, Animal Cells, Medicine, Basic Cancer Research, Drug Research and Development, Biomacromolecule-Ligand Interactions, Q, Induced apoptosis, R, Cell Biology, Biochemistry, Science, Medicine and Health Sciences, N-MYC, Small Molecules
54 references, page 1 of 4

1 Vita M, Henriksson M (2006) The Myc oncoprotein as a therapeutic target for human cancer. Semin Cancer Biol 16: 318–330.16934487 [PubMed]

2 Meyer N, Penn LZ (2008) Reflecting on 25 years with MYC. Nat Rev Cancer 8: 976–990.19029958 [PubMed]

3 Luscher B, Larsson LG (1999) The basic region/helix-loop-helix/leucine zipper domain of Myc proto-oncoproteins: function and regulation. Oncogene 18: 2955–2966.10378692 [PubMed]

4 Malynn BA, de Alboran IM, O'Hagan RC, Bronson R, Davidson L, et al (2000) N-myc can functionally replace c-myc in murine development, cellular growth and differentiation. Genes and Dev 14: 1390–1399.10837031 [OpenAIRE] [PubMed]

5 Downs KM, Martin GR, Bishop JM (1989) Contrasting patterns of myc and N-myc expression during gastrulation of the mouse embryo. Genes Dev 3: 860–869.2663644 [PubMed]

6 Zimmerman KA, Yancopoulos GD, Collum RG, Smith RK, Kohl NE, et al (1986) Differential expression of myc family genes during murine development. Nature 319: 780–783.2419762 [PubMed]

7 Hirvonen H, Makela TP, Sandberg M, Kalimo H, Vuorio E, et al (1990) Expression of the myc proto-oncogenes in developing human fetal brain. Oncogene 5: 1787–1797.2284098 [PubMed]

8 Mugrauer G, Alt FW, Ekblom P (1988) N-myc proto-oncogene expression during organogenesis in the developing mouse as revealed by in situ hybridization. J Cell Biol 107: 1325–1335.3049618 [OpenAIRE] [PubMed]

9 Stanton BR, Parada LF (1992) The N-myc proto-oncogene: developmental expression and in vivo site-directed mutagenesis. Brain Pathol 2: 71–83.1341949 [PubMed]

10 Albihn A, Johnsen JI, Henriksson MA (2010) MYC in oncogenesis and as a target for cancer therapies. Adv Cancer Res 107: 163–224.20399964 [PubMed]

11 Brodeur GM (2003) Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer 3: 203–216.12612655 [PubMed]

12 Maris JM, Hogarty MD, Bagatell R, Cohn SL (2007) Neuroblastoma. Lancet 369: 2106–2120.17586306 [PubMed]

13 Larsson LG, Henriksson MA (2010) The Yin and Yang f unctions of the Myc oncoprotein in cancer development and as targets for therapy. Exp Cell Res 316: 1429–1437.20382143 [PubMed]

14 Prochownik EV, Vogt PK (2010) Therapeutic Targeting of Myc. Genes Cancer 1: 650–659.21132100 [OpenAIRE] [PubMed]

15 Felsher DW (2010) MYC Inactivation Elicits Oncogene Addiction through Both Tumor Cell-Intrinsic and Host-Dependent Mechanisms. Genes Cancer 1: 597–604.21037952 [OpenAIRE] [PubMed]

54 references, page 1 of 4
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publication . Article . 2014

Targeting of the MYCN protein with small molecule c-MYC inhibitors.

Müller, Inga; Larsson, Karin; Frenzel, Anna; Oliynyk, Ganna; Zirath, Hanna; Prochownik, Edward V.; Westwood, Nicholas J.; Henriksson, Marie Arsenian;