Temporal Evolution of Cellular Heterogeneity during the Progression to Advanced AR-Negative Prostate Cancer

Single-cell-based approaches revealed striking temporal changes to the transcriptome and chromatin accessibility which have identified the emergence of distinct cell populations, marked by differential expression of Ascl1 and Pou2f3, during the transition to neuroendocrine prostate cancer.
[Nature Communications]
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Concurrent Targeting of MAP3K3 and BRD4 by miR-3140-3p Overcomes Acquired Resistance to BET Inhibitors in Neuroblastoma Cells

Investigators demonstrated that miR-3140-3p suppresses tumor cell growth in MYCN-amplified NB by downregulating MYCN and MYC through BRD4 suppression.
[Molecular Therapy-Nucleic Acids]
Liu, C., Gen, Y., Tanimoto, K., Muramatsu, T., Inoue, J., & Inazawa, J. (2021). Concurrent targeting of MAP3K3 and BRD4 by miR-3140-3p overcomes acquired resistance to BET inhibitors in neuroblastoma cells. Molecular Therapy - Nucleic Acids, 0(0). https://doi.org/10.1016/j.omtn.2021.05.001 Cite
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Catastrophic ATP Loss Underlies a Metabolic Combination Therapy Tailored for MYCN-Amplified Neuroblastoma

Investigators demonstrated that MYCN–amplified neuroblastomas were sensitive to the combined inhibition of MCT1 and complex I of the mitochondrion.
[Proceedings of the National Academy of Sciences of the United States of America]
Dalton, K. M., Lochmann, T. L., Floros, K. V., Calbert, M. L., Kurupi, R., Stein, G. T., McClanaghan, J., Murchie, E., Egan, R. K., Greninger, P., Dozmorov, M., Ramamoorthy, S., Puchalapalli, M., Hu, B., Shock, L., Koblinski, J., Glod, J., Boikos, S. A., Benes, C. H., & Faber, A. C. (2021). Catastrophic ATP loss underlies a metabolic combination therapy tailored for MYCN-amplified neuroblastoma. Proceedings of the National Academy of Sciences, 118(13). https://doi.org/10.1073/pnas.2009620118 Cite
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An ALYREF-MYCN Coactivator Complex Drives Neuroblastoma Tumorigenesis through Effects on USP3 and MYCN Stability

The authors identified ALYREF, expressed from the most common genetic copy number variation in neuroblastoma, chromosome 17q21-ter gain as a key regulator of MYCN protein turnover.
[Nature Communications]
Nagy, Z., Seneviratne, J. A., Kanikevich, M., Chang, W., Mayoh, C., Venkat, P., Du, Y., Jiang, C., Salib, A., Koach, J., Carter, D. R., Mittra, R., Liu, T., Parker, M. W., Cheung, B. B., & Marshall, G. M. (2021). An ALYREF-MYCN coactivator complex drives neuroblastoma tumorigenesis through effects on USP3 and MYCN stability. Nature Communications, 12(1), 1881. https://doi.org/10.1038/s41467-021-22143-x Cite
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A Novel Combination Therapy Targeting Ubiquitin-Specific Protease 5 in MYCN-Driven Neuroblastoma

Effects of drug combinations on cell viability, proliferation, apoptosis and colony forming were assessed in a panel of neuroblastoma cell lines.
[Oncogene]
Cheung, B. B., Kleynhans, A., Mittra, R., Kim, P. Y., Holien, J. K., Nagy, Z., Ciampa, O. C., Seneviratne, J. A., Mayoh, C., Raipuria, M., Gadde, S., Massudi, H., Wong, I. P. L., Tan, O., Gong, A., Suryano, A., Diakiw, S. M., Liu, B., Arndt, G. M., … Marshall, G. M. (2021). A novel combination therapy targeting ubiquitin-specific protease 5 in MYCN-driven neuroblastoma. Oncogene, 1–15. https://doi.org/10.1038/s41388-021-01712-w Cite
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GAS7 Deficiency Promotes Metastasis in MYCN-Driven Neuroblastoma

Researchers showed that the growth arrest-specific 7 (GAS7) gene, located at chromosome band 17p13.1, is preferentially deleted in high-risk MYCN-driven neuroblastoma.
[Cancer Research]
Dong, Z., Yeo, K. S., Lopez, G., Zhang, C., Eggum, E. N. D., Rokita, J. L., Ung, C. Y., Levee, T. M., Her, Z. P., Howe, C. J., Hou, X., Ree, J. H. van, Li, S., He, S., Tao, T., Fritchie, K., Torres-Mora, J., Lehman, J. S., Meves, A., … Zhu, S. (2021). GAS7 Deficiency Promotes Metastasis in MYCN-driven Neuroblastoma. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-1890 Cite
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Single-Cell Atlas of Developing Murine Adrenal Gland Reveals Relation of Schwann Cell Precursor Signature to Neuroblastoma Phenotype

Investigators provided an insight into the developing adrenal gland and introduced the Schwann cell precursor gene signature as being of interest for further research in understanding neuroblastoma phenotype.
[Proceedings of the National Academy of Sciences of the United States of America]
Hanemaaijer, E. S., Margaritis, T., Sanders, K., Bos, F. L., Candelli, T., Al-Saati, H., Noesel, M. M. van, Meyer-Wentrup, F. A. G., Wetering, M. van de, Holstege, F. C. P., & Clevers, H. (2021). Single-cell atlas of developing murine adrenal gland reveals relation of Schwann cell precursor signature to neuroblastoma phenotype. Proceedings of the National Academy of Sciences, 118(5). https://doi.org/10.1073/pnas.2022350118 Cite
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ALK Ligand ALKAL2 Potentiates MYCN-Driven Neuroblastoma in the Absence of ALK Mutation

Scientists tested whether anaplastic lymphoma kinase AL2 (ALKAL2) ligand could potentiate neuroblastoma progression in the absence of ALK mutation
[EMBO Journal]
Borenäs, M., Umapathy, G., Lai, W.-Y., Lind, D. E., Witek, B., Guan, J., Mendoza-Garcia, P., Masudi, T., Claeys, A., Chuang, T.-P., El Wakil, A., Arefin, B., Fransson, S., Koster, J., Johansson, M., Gaarder, J., Van den Eynden, J., Hallberg, B., & Palmer, R. H. (2021). ALK ligand ALKAL2 potentiates MYCN-driven neuroblastoma in the absence of ALK mutation. The EMBO Journal, n/a(n/a), e105784. https://doi.org/10.15252/embj.2020105784 Cite
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Nerve Growth Factor Interacts with CHRM4 and Promotes Neuroendocrine Differentiation of Prostate Cancer and Castration Resistance

The authors showed that an androgen-deprivation therapy-stimulated transcription factor, ZBTB46, upregulated NGF via ZBTB46 mediated-transcriptional activation of nerve growth factor.
[Communications Biology]

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18F-Meta-Fluorobenzylguanidine (18F-mFBG) to Monitor Changes in Norepinephrine Transporter Expression in Response to Therapeutic Intervention in Neuroblastoma Models

Researchers investigated the potential of 18F-mFBG, a positron emission tomography analogue of the 123I-mIBG radiotracer, to quantify norepinephrine transporter expression levels in mouse models of neuroblastoma following treatment with AZD2014, a dual mTOR inhibitor.
[Scientific Reports]
Turnock, S., Turton, D. R., Martins, C. D., Chesler, L., Wilson, T. C., Gouverneur, V., Smith, G., & Kramer-Marek, G. (2020). 18 F-meta-fluorobenzylguanidine ( 18 F-mFBG) to monitor changes in norepinephrine transporter expression in response to therapeutic intervention in neuroblastoma models. Scientific Reports, 10(1), 20918. https://doi.org/10.1038/s41598-020-77788-3 Cite
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Enhancer Hijacking Determines Extrachromosomal Circular MYCN Amplicon Architecture in Neuroblastoma

Scientists analyzed the MYCN amplicon structure using short-read and Nanopore sequencing and its chromatin landscape using ChIP-seq, ATAC-seq and Hi-C. This reveals two distinct classes of amplicons which explain the regulatory requirements for MYCN overexpression.
[Nature Communications]
Helmsauer, K., Valieva, M. E., Ali, S., Chamorro González, R., Schöpflin, R., Röefzaad, C., Bei, Y., Dorado Garcia, H., Rodriguez-Fos, E., Puiggròs, M., Kasack, K., Haase, K., Keskeny, C., Chen, C. Y., Kuschel, L. P., Euskirchen, P., Heinrich, V., Robson, M. I., Rosswog, C., … Koche, R. P. (2020). Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma. Nature Communications, 11(1), 5823. https://doi.org/10.1038/s41467-020-19452-y Cite
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