Article
Chemistry, Multidisciplinary
Xin Peng, Shaolu Zhang, Yingying Wang, Zhicheng Zhou, Zixiang Yu, Zhenxing Zhong, Liang Zhang, Zhe-Sheng Chen, Francois X. Claret, Moshe Elkabets, Feng Wang, Fan Sun, Ran Wang, Han Liang, Hou-Wen Lin, Dexin Kong
Summary: The triterpene compound STELB enhances the sensitivity of GBM to DNA-damaging treatments by inhibiting the expression of HR factors and can penetrate the blood-brain barrier to exert anti-GBM effects.
Article
Oncology
Waaqo Daddacha, Dominique Monroe, Kristen Carver, Edidiong R. Usoro, Ahmet Alptekin, Hongyan Xu, Satoru Osuka, Ali S. Arbab, Daitoku Sakamuro
Summary: Glioblastoma is a common and lethal primary brain tumor with limited treatment options. Depleting the SAMHD1 protein can enhance the sensitivity of glioblastoma to radiation and temozolomide, and viral protein X (Vpx) may serve as a therapeutic tool.
Article
Cell Biology
Alessandro Tancredi, Olga Gusyatiner, Pierre Bady, Michelle C. Buri, Remy Lomazzi, Davide Chiesi, Mahmoud Messerer, Monika E. Hegi
Summary: Bromodomain and extra-terminal tail (BET) proteins are potential epigenetic targets in cancer, including glioblastoma. BET inhibitors disrupt the histone code-gene transcription link. BET-induced differential gene expression in glioblastoma derived-spheres revealed 6 distinct response patterns. The O-6-methylguanine-DNA methyltransferase (MGMT) gene, a known resistance factor for glioblastoma treatment, showed consistent downregulation in response to BET inhibitors.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Alexandra M. Amen, Christof Fellmann, Katarzyna M. Soczek, Shawn M. Ren, Rachel J. Lew, Gavin J. Knott, Jesslyn E. Park, Andrew M. McKinney, Andrew Mancini, Jennifer A. Doudna, Joseph F. Costello
Summary: Mutations in the TERT promoter of glioblastomas create binding sites for GABP transcription factor complexes, leading to reactivation of TERT and maintenance of telomeres. GBM cells with TERT promoter mutations display a dependence on GABPB1L for proliferation, which can be rescued by upregulation of the protein paralogue GABPB2. Inhibition of GABPB1L in combination with chemotherapy results in reduced growth of intracranial GBM tumors by impairing DNA damage response.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Zheng-Cheng Yu, Tianhe Li, Ellen Tully, Peng Huang, Chih-Ning Chen, Philipp Oberdoerffer, Stephanie Gaillard, Ie-Ming Shih, Tian-Li Wang
Summary: ARID1A is a subunit of SWI/SNF chromatin remodeling complexes and is frequently mutated in various types of human cancers, especially those originating from endometrial epithelium. Loss-of-function mutations in ARID1A affect epigenetic regulation, cell-cycle checkpoint control, and DNA damage repair. This study demonstrates that ARID1A-deficient cells harbor DNA base lesions and impaired base excision repair. Furthermore, the combination of temozolomide and PARP inhibitors effectively induces DNA damage and suppresses tumor growth in ARID1A-mutated cancers.
Article
Biology
Luis Gregory Zamalloa, Margaret M. Pruitt, Nicole M. Hermance, Himabindu Gali, Rachel L. Flynn, Amity L. Manning
Summary: This study investigates the impact of RB dysfunction on genome stability and whether this change can be exploited in RB-deficient cancer cells. The findings demonstrate that RB loss leads to high levels of PARylation, and inhibiting PARylation allows RB-deficient cells to progress to mitosis despite replication stress. These defects result in high levels of DNA damage and compromised cell viability. Therefore, drugs targeting PARP1 and PARP2 may have clinical relevance in the treatment of RB-deficient cancers.
LIFE SCIENCE ALLIANCE
(2023)
Article
Biochemistry & Molecular Biology
Neerada Meenakshi Warrier, Ramesh Kumar Krishnan, Vijendra Prabhu, Raghu Chandrashekhar Hariharapura, Prasoon Agarwal, Praveen Kumar
Summary: This study identifies survivin as a significant biomarker for glioblastoma multiforme cancer stem cells (GSCs) and demonstrates its importance in stemness, cancer progression, and therapy resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Jingru Che, Thomas J. DePalma, Hemamylammal Sivakumar, Louisa S. Mezache, Miranda M. Tallman, Monica Venere, Katelyn Swindle-Reilly, Rengasayee Veeraraghavan, Aleksander Skardal
Summary: Glioblastoma (GBM) is a common and aggressive form of brain cancer with poor prognosis due to resistance to the most commonly used chemotherapy. Recent studies have shown that high expression of connexin 43 (Cx43) in GBM is associated with worse patient outcomes. In this study, researchers used a three-dimensional organoid model to demonstrate that combined treatment with a Cx43 mimetic peptide, alpha CT1, and TMZ significantly improved treatment efficacy for certain populations of GBM. These findings suggest that inhibiting Cx43 could be a promising approach for improving GBM treatment.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Oncology
Xiaoqing Fan, Suling Sun, Haoran Yang, Huihui Ma, Chenggang Zhao, Wanxiang Niu, Junqi Fan, Zhiyou Fang, Xueran Chen
Summary: This study reveals the inactivation of the ZDHHC16/SETD2/H3K36me3 signaling axis in EGFR-altered GBM, which affects DNA damage repair signaling. The depalmitoylation inhibitor, PalmB, shows potential as a novel adjuvant treatment for GBM patients undergoing radiation therapy.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)
Article
Oncology
Jihong Xu, Pei-Jung Wu, Tzung-Huei Lai, Pratibha Sharma, Alessandro Canella, Alessandra M. Welker, Christine E. Beattie, J. Brad Elder, Michelle Easley, Russell Lonser, Naduparambil K. Jacob, Maciej Pietrzak, Cynthia M. Timmers, Frederick Lang, Deepa Sampath, Vinay K. Puduvalli
Summary: Targeting HR by HSP90 inhibition sensitizes GSCs to radiation and chemotherapy, leading to extended survival in GBM models.
CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Katharina Otte, Kai Zhao, Madita Braun, Andreas Neubauer, Hartmann Raifer, Frederik Helmprobst, Felipe Ovalle Barrera, Christopher Nimsky, Joerg W. Bartsch, Tillmann Rusch
Summary: This study found that Eltanexor, a second-generation XPO1 inhibitor, has effective monotherapy effects on GBM cells and can be combined with current adjuvant therapies to provide a more effective treatment for GBM. The mechanism of Eltanexor-induced apoptosis in GBM cells may be related to increased expression of TP53-dependent genes.
Article
Oncology
Tuyen T. Dang, Julio C. Morales
Summary: CENP-I is a crucial component of the inner kinetochore, essential for proper chromosomal segregation during mitosis and DNA double-strand break repair. Loss of CENP-I leads to impaired DSB repair, reduced cellular survival, and correlates with poor patient prognosis in gliomas.
Article
Oncology
Beiwu Lan, Hongyang Zhao, Yichun He, Zenghui Zhao, Nang Wang, Yufei Gao
Summary: This study found that inhibition of HsPDF can suppress the expression of mtDNA-encoded proteins in GBM cells, and promote mitochondrial apoptosis by decreasing OXPHOS level, disrupting mitochondrial protein homeostasis, increasing mitochondrial fission and activating the integrated stress response.
EXPERIMENTAL CELL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Mi Ae Kang, Jong-Soo Lee
Summary: CTCF, a highly conserved multifunctional DNA-binding protein with 11 zinc fingers, plays crucial roles in diverse genomic processes such as transcriptional regulation, insulation, genome imprinting, and maintenance of genome organization. Recent findings reveal that CTCF is involved in DNA double-strand break (DSB) repair through homologous recombination (HR), facilitating accurate restoration of broken DNA sequences. Understanding the functional crosstalks between CTCF and other HR factors may shed light on the molecular basis of various human diseases and the diverse functions of CTCF in genome biology.
Article
Cell Biology
Nan Wang, Renxuan Huang, Kunmeng Yang, Yichun He, Yufei Gao, Delu Dong
Summary: Glioblastoma multiforme (GBM) is a highly malignant primary tumor of the central nervous system (CNS) with decreasing sensitivity to chemotherapy over time. Research has shown that under TMZ treatment, the oxidative phosphorylation (OXPHOS) level in GBM cells increases, influenced by factors such as mitochondrial morphology and AMPK.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)