Article
Oncology
Krista M. Dalton, Kateryna Krytska, Timothy L. Lochmann, Renata Sano, Colleen Casey, Alessia D'Aulerio, Qasim A. Khan, Giovanna Stein Crowther, Colin Coon, Jinyang Cai, Sheeba Jacob, Richard Kurupi, Bin Hu, Mikhail Dozmorov, Patricia Greninger, Andrew J. Souers, Cyril H. Benes, Yael P. Mosse, Anthony C. Faber
Summary: Venetoclax shows limited single-agent activity in MYCN-amplified neuroblastoma but can be potentiated by rational combinations with MDM2 inhibitor, MCL-1 inhibitor, or standard-of-care drugs like cyclophosphamide and topotecan. These combinations have demonstrated synergistic cell killing in preclinical models and hold promise for improving treatment efficacy in patients with amplified MYCN neuroblastoma.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Oncology
Tao Liu, Lubing Gu, Zhongzhi Wu, Najah Albadari, Wei Li, Muxiang Zhou
Summary: Amplification of MYCN gene leads to overexpression of MYCN mRNA and protein, which plays a role in promoting neuroblastoma. A small molecule compound MX25-1 can bind to the 3'UTR of MYCN mRNA and induce its degradation, resulting in cell growth inhibition and cell death specifically in MYCN-amplified neuroblastoma cells. The activation of tumor suppressor miRNA let-7 is associated with the anticancer activity of MX25-1.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Atif Zafar, Wei Wang, Gang Liu, Wa Xian, Frank McKeon, Jia Zhou, Ruiwen Zhang
Summary: Neuroblastoma poses a significant challenge in pediatric oncology, with p53 protein playing a key protective role against genome instability. Overexpression of MDM2 in neuroblastoma can lead to p53 inhibition, drug resistance, and other non-canonical p53 functions. Research is focused on restoring p53 function by targeting the p53-MDM2 axis for potential therapeutic strategies.
Article
Biochemistry & Molecular Biology
Erhan Aptullahoglu, Carmela Ciardullo, Jonathan P. Wallis, Helen Marr, Scott Marshall, Nick Bown, Elaine Willmore, John Lunec
Summary: This study investigates the effects of splicing modulation on key proteins in the p53 signaling pathway. The results show that splicing modulation by E7107 reduces full-length MDM2 production and increases p53 expression in TP53(WT) cells. Additionally, a novel isoform of p21(WAF1) with compromised kinase inhibitory activity is produced due to intron retention. E7107 synergizes with the MDM2 inhibitor RG7388, leading to greater p53 stabilization and apoptosis. This study provides evidence for a novel combination therapy of MDM2 and spliceosome inhibitors for the treatment of CLL and other hematological malignancies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Irene Veneziani, Paola Infante, Elisa Ferretti, Ombretta Melaiu, Cecilia Battistelli, Valeria Lucarini, Mirco Compagnone, Carmine Nicoletti, Aurora Castellano, Stefania Petrini, Marzia Ognibene, Annalisa Pezzolo, Lucia Di Marcotullio, Roberto Bei, Lorenzo Moretta, Vito Pistoia, Doriana Fruci, Vincenzo Barnaba, Franco Locatelli, Loredana Cifaldi
Summary: The study demonstrated that Nutlin-3a could enhance NK cell-mediated killing of neuroblastoma cells by restoring p53 function and increasing ligand expression for NK-ARs. Adoptive transfer of human NK cells into neuroblastoma-bearing mice resulted in tumor shrinkage and improved overall survival. Nutlin-3a also boosted NK cell-mediated cytotoxicity against neuroblastoma spheroids by increasing ligand expression in primary neuroblastoma cells.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Akiko Fujimura, Hisashi Ishida, Tamiko Nozaki, Shuhei Terada, Yuto Azumaya, Tadashi Ishiguro, Yugo R. Kamimura, Tomoya Kujirai, Hitoshi Kurumizaka, Hidetoshi Kono, Kenzo Yamatsugu, Shigehiro A. Kawashima, Motomu Kanai
Summary: Peptides can be modified and used as ligands for targeting proteins of interest by inserting them into fusion proteins. This study demonstrates the use of a peptide ligand-inserted fusion protein as a universal adaptor for targeting proteins with cell-permeable and stable small molecules. By using specific small molecules, post-translational modifications can be targeted to specific residues on the proteins.
ACS CENTRAL SCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Soraya Epp, Shin Mei Chuah, Melinda Halasz
Summary: This review examines the intricate interplay between MYCN and known epigenetic mechanisms in neuroblastoma, and provides insights into emerging therapeutic strategies targeting these mechanisms to improve patient outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Jorg Otte, Cecilia Dyberg, Adena Pepich, John Inge Johnsen
Summary: Dysregulated expression of the transcription factor MYCN is frequently detected in nervous system tumors such as childhood neuroblastoma and is a strong predictor of poor prognosis. Increased MYCN expression is an early event in these cancers, leading to a peculiar dysregulation of cells that exhibit embryonal or cancer stem-like qualities.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Hai-Feng Zhang, Alberto Delaidelli, Sumreen Javed, Busra Turgu, Taylor Morrison, Christopher S. Hughes, Xiaqiu Yang, Manideep Pachva, Michael M. Lizardo, Gurdeep Singh, Jennifer Hoffmann, Yue Zhou Huang, Khushbu Patel, Rawan Shraim, Sonia H. Y. Kung, Gregg B. Morin, Samuel Aparicio, Daniel Martinez, John M. Maris, Kristopher R. Bosse, Karla C. Williams, Poul H. Sorensen
Summary: This study reveals that GREB1 gene, located near MYCN locus, is frequently coexpressed with MYCN and promotes cell survival in high-risk neuroblastoma (NB). The research also identifies MYO1B gene as a crucial regulator of invasion and metastasis in MYCN amplified NB. Furthermore, MYO1B is found to regulate secretome reprogramming and the cytokine MIF mediates its pro-invasive and pro-metastatic activity.
Review
Cell Biology
Kiyohiro Ando, Akira Nakagawara
Summary: The RUNX family plays a crucial role in neural crest cell differentiation and may also be involved in neuroblastoma tumorigenesis. Its function in tumor development can vary depending on the specific context, including the response to chemotherapy. In primary neuroblastomas, RUNX3 acts as a tumor suppressor, while RUNX1 regulates cell proliferation in a dual manner influenced by genetic and epigenetic factors, including MYCN. This review focuses on the mechanism through which the RUNX family regulates neurotrophin receptors (Trk family) associated with neuroblastoma aggressiveness, as well as their potential involvement in functional alterations of the p53 family members in neuroblastoma tumorigenesis. Understanding the contribution of the RUNX family to neuroblastoma tumorigenesis is crucial for future molecular-based therapies.
Review
Oncology
Swapnil Parashram Bhavsar
Summary: Oncogenic drivers like MYCN in neuroblastoma subsets pose a significant challenge due to their strong correlation with high-risk metastatic disease and poor prognosis. However, the functional role of MYCN and its regulatory partners in neuroblastoma metastasis has only been partially elucidated. This minireview summarizes the recent progress in understanding their roles.
FRONTIERS IN ONCOLOGY
(2023)
Article
Chemistry, Medicinal
Idoia Blanco-Luquin, Paula Lazcoz, Jon Celay, Javier S. Castresana, Ignacio J. Encio
Summary: Research on the alterations in the p53/MDM2/p14ARF signaling pathway in neuroblastoma cell lines is crucial for understanding drug resistance and differentiation agent efficacy. The results suggest that TP53 mutated SK-N-FI cells respond better to retinoic acid isomers.
Review
Oncology
Mohit Bansal, Anamika Gupta, Han-Fei Ding
Summary: Metabolic reprogramming plays a crucial role in high-risk neuroblastoma and offers potential therapeutic opportunities. This review summarizes the recent progress in understanding neuroblastoma metabolic reprogramming and highlights important areas for future research.
Article
Oncology
Zhiwei Dong, Kok Siong Yeo, Gonzalo Lopez, Cheng Zhang, Erin N. Dankert Eggum, Jo Lynne Rokita, Choong Yong Ung, Taylor M. Levee, Zuag Paj Her, Cassie J. Howe, Xiaonan Hou, Janine H. van Ree, Shuai Li, Shuning He, Ting Tao, Karen Fritchie, Jorge Torres-Mora, Julia S. Lehman, Alexander Meves, Gina L. Razidlo, Komal S. Rathi, S. John Weroha, A. Thomas Look, Jan M. van Deursen, Hu Li, Jennifer J. Westendorf, John M. Maris, Shizhen Zhu
Summary: Research has shown that GAS7 gene is preferentially deleted in high-risk MYCN-driven neuroblastoma, and its deficiency accelerates metastasis in neuroblastoma models. Loss of GAS7 affects cell-cell interaction and contact among tumor cells, identifying a novel mechanism underlying tumor metastasis in MYCN-driven neuroblastoma.
Article
Multidisciplinary Sciences
Jing Zhao, Alan Blayney, Xiaorong Liu, Lauren Gandy, Weihua Jin, Lufeng Yan, Jeung-Hoi Ha, Ashley J. Canning, Michael Connelly, Chao Yang, Xinyue Liu, Yuanyuan Xiao, Michael S. Cosgrove, Sozanne R. Solmaz, Yingkai Zhang, David Ban, Jianhan Chen, Stewart N. Loh, Chunyu Wang
Summary: Epigallocatechin gallate (EGCG) in green tea induces apoptosis in cancerous cells through a direct interaction with the tumor suppressor p53, inhibiting p53 ubiquitination by its regulatory E3 ligase MDM2 and stabilizing p53 for anti-tumor activity.
NATURE COMMUNICATIONS
(2021)
