Review
Biochemistry & Molecular Biology
Hyunkoo Kang, Haksoo Lee, Dahye Kim, Byeongsoo Kim, JiHoon Kang, Hae Yu Kim, HyeSook Youn, BuHyun Youn
Summary: Glioblastoma (GBM) is a highly malignant brain tumor that is resistant to current therapies. This review focuses on the resistance mechanisms of GBM, particularly towards temozolomide (TMZ), and summarizes the recent findings on the intrinsic and extrinsic mechanisms of chemoresistance in GBM stem cells (GSCs). It also discusses novel therapeutic strategies, such as molecular targeting, autophagy inhibition, oncolytic viral therapy, drug repositioning, and targeting of GSC niches, to eliminate GSCs and improve GBM therapy.
Article
Biochemistry & Molecular Biology
Zhourui Ma, Shizhong Cai, Qianwei Xiong, Wei Liu, Hongliang Xia, Zhenhong Zhu, Zhijian Huang, Xiangming Yan, Qian Wang
Summary: This study reveals the role of WNT signaling in the chemoresistance of glioblastoma multiforme (GBM) to temozolomide (TMZ). The loss of function of p53 in GBM downregulates miR-34a expression, leading to the activation of WNT signaling and the resistance to TMZ. By targeting the miR-34a/WNT6 axis, drug sensitivity of p53-mutant GBM cells can be restored and overall survival can be extended.
Article
Biochemistry & Molecular Biology
Parveen Kumar, Vivek Verma, Dheeraj Mohania, Surbhi Gupta, Avneet K. Babbar, Bhawna Rathi, Rakesh S. Dhanda, Manisha Yadav
Summary: The study revealed that RUNX1T1 is mutated in different cancers and associated with poor overall survival in glioma patients, possibly affecting glioma growth and development through HIF1α regulation. Experimental results showed that downregulation of RUNX1T1 may lead to degradation of HIF1α, reducing proliferation and invasiveness of glioblastoma cells.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Huaijin Zhang, Yuling Chen, Xiaohui Liu, Haiteng Deng
Summary: This study found that mitochondrial dysfunction, rotenone treatment, elevated Ca2+ levels, and activation of the JNK-STAT3 pathway all contribute to increased resistance of glioblastoma to TMZ. Inhibiting JNK or STAT3 can increase sensitivity to TMZ. Co-administration of TMZ with a JNK or STAT3 inhibitor holds promise as an effective treatment for glioblastoma.
Review
Oncology
Xiaoteng Cui, Yunfei Wang, Junhu Zhou, Qixue Wang, Chunsheng Kang
Summary: Malignant gliomas are difficult to diagnose and treat due to their infiltrative growth pattern, rapid progression, and poor prognosis. Temozolomide (TMZ) is the only first-line chemotherapeutic drug for malignant gliomas that can cross the blood-brain barrier, but some patients are insensitive to TMZ and can develop acquired resistance during treatment.
CANCER BIOLOGY & MEDICINE
(2023)
Article
Oncology
Shuai Yuan, Qi Yan, Zhi-Yong Zhao, Jing-Long Zhang, He Zhang, Hang Yin, Zhi Yuan
Summary: The study revealed that LINC00520 is overexpressed in GBM, contributing to resistance to TMZ. Silencing LINC00520 or interacting with RNA-binding protein LIN28B can effectively inhibit tumor growth and enhance sensitivity to TMZ.
CANCER CELL INTERNATIONAL
(2022)
Article
Pharmacology & Pharmacy
Maria Chiara Proto, Donatella Fiore, Chiara Piscopo, Chiara Laezza, Maurizio Bifulco, Patrizia Gazzerro
Summary: GBM is the most common and lethal primary malignant brain tumor, and its management is challenging. IPA and N6-BA affect GBM cell proliferation by modulating FBXW7 expression and enhancing TMZ killing effect by downregulating MGMT expression.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kai Zhao, Agnes Schaefer, Zhuo Zhang, Katharina Elsaesser, Carsten Culmsee, Li Zhong, Axel Pagenstecher, Christopher Nimsky, Joerg W. Bartsch
Summary: Carbonic anhydrase CA2 is highly expressed in recurrent glioblastoma and temozolomide-resistant glioblastoma stem-like cells (GSCs), promoting cell invasion. The CA2 inhibitor brinzolamide is more effective than the pan-CA inhibitor acetazolamide in sensitizing GSCs to TMZ-induced cell death. The combined treatment of TMZ and brinzolamide induces autophagy in GBM cell lines and GSCs, suggesting a potential treatment strategy for tackling GBM chemoresistance and recurrence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Luca X. Zampieri, Martina Sboarina, Andrea Cacace, Debora Grasso, Leopold Thabault, Loic Hamelin, Thibaut Vazeille, Elodie Dumon, Rodrigue Rossignol, Raphael Frederick, Etienne Sonveaux, Florence Lefranc, Pierre Sonveaux
Summary: The study found that mitochondria in glioblastoma cells become fitter in response to chemotherapy, leading to chemoresistance. By inhibiting oxidative phosphorylation and/or autophagy/mitophagy, this resistance can be targeted. Some PARP inhibitors were also found to be inhibitors of mitochondrial Complex I.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jose-Dellis Rocha, Daniel Uribe, Javiera Delgado, Ignacio Niechi, Sebastian Alarcon, Jose Ignacio Erices, Romulo Melo, Rodrigo Fernandez-Gajardo, Flavio Salazar-Onfray, Rody San Martin, Claudia Quezada Monras
Summary: This study found that Glioblastoma stem-like cells (GSCs) in hypoxic environments exhibit increased chemoresistance due to the induction of adenosine/MRP signaling pathway, leading to enhanced expression and extrusion capacity of MRP3. The activation of the A2B adenosine receptor promotes GSC survival through MRP3 induction. These findings provide new insights into understanding and overcoming chemoresistance in GSCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Jianxing Yin, Xin Ge, Zhumei Shi, Chen Yu, Chenfei Lu, Yutian Wei, Ailiang Zeng, Xiefeng Wang, Wei Yan, Junxia Zhang, Yongping You
Summary: The study found that EVs from hypoxic GSCs exerted a greater impact on GBM chemoresistance, with significantly upregulated miR-30b-3p. HIF1 alpha and STAT3 transcriptionally induced miR-30b-3p expression, while hnRNPA2B1 facilitated its transfer into EVs, targeting RHOB and reducing apoptosis while promoting proliferation in vitro and in vivo. The findings suggest that targeting EV-miR-30b-3p could be a potential treatment strategy for GBM.
Editorial Material
Biochemistry & Molecular Biology
Kirit Singh, Kelly M. Hotchkiss, Ian F. Parney, John De Groot, Solmaz Sahebjam, Nader Sanai, Michael Platten, Evanthia Galanis, Michael Lim, Patrick Y. Wen, Giuseppe Minniti, Howard Colman, Timothy F. Cloughesy, Minesh P. Mehta, Marjolein Geurts, Isabel Arrillaga-Romany, Annick Desjardins, Kirk Tanner, Susan Short, David Arons, Elizabeth Duke, Wolfgang Wick, Stephen J. Bagley, David M. Ashley, Priya Kumthekar, Roel Verhaak, Anthony J. Chalmers, Anoop P. Patel, Colin Watts, Peter E. Fecci, Tracy T. Batchelor, Michael Weller, Michael A. Vogelbaum, Matthias Preusser, Mitchel S. Berger, Mustafa Khasraw
Summary: A breakthrough in drug discovery for glioblastoma necessitates the consecutive collection of central nervous system tissue through window of opportunity trials.
Article
Biochemistry & Molecular Biology
Dana Hellmold, Carolin Kubelt, Tina Daunke, Silje Beckinger, Ottmar Janssen, Margarethe Hauck, Fabian Schuett, Rainer Adelung, Ralph Lucius, Jochen Haag, Susanne Sebens, Michael Synowitz, Janka Held-Feindt
Summary: Glioblastoma (GBM) is a difficult-to-treat disease with high resistance to chemotherapy and radiotherapy. This study investigated the chemoresistance mechanisms of surviving GBM cells and the effects of combination therapy with temozolomide (TMZ) and AT101. The results showed that while the combination therapy was highly efficient, it led to the predominance of phosphatidylserine-positive GBM cells over time. Analysis revealed phosphorylation of AKT, mTOR, and GSK3beta, resulting in the induction of pro-tumorigenic genes in surviving GBM cells. Treatment with Torin2 partially counteracted the observed effects, and the combination therapy also altered the composition of extracellular vesicles released from surviving GBM cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Deniz Caylioglu, Rieke Johanna Meyer, Dana Hellmold, Carolin Kubelt, Michael Synowitz, Janka Held-Feindt
Summary: The study demonstrates the potent cytotoxic effects of AT101 on GBM stem-like cells, especially upon co-culture with stem-like cell-conditioned medium. This treatment approach may prevent GBM recurrences by inhibiting specific signaling pathways and regulating receptor expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jin Liang, Jing Sun, Aibin Liu, Lei Chen, Xiaofang Ma, Xiaozhi Liu, Chunyan Zhang
Summary: This study found that Saikosaponin D (SSD) has antitumor activity against glioblastoma cells and can enhance the chemotherapy effect of temozolomide (TMZ). Additionally, SSD can inhibit the stemness maintenance potential of glioblastoma cells. The research provides a theoretical basis for the application of SSD in overcoming chemotherapy resistance in glioblastoma and offers a new hope for clinical treatment.
BIOCHEMISTRY AND BIOPHYSICS REPORTS
(2022)