The Influence of EGFR Inactivation on the Radiation Response in High Grade Glioma

Alexandru, Oana; Purcaru, Ștefana Oana; Tătăranu, Ligia Gabriela; Lucan, Laura; Castro, Juan; Folcuţi, Catalin; Artene, Ştefan-Alexandru; Tuta, Cristian; Dricu, Anica

doi:10.3390/ijms19010229

Cited by 17 publications

(18 citation statements)

References 46 publications

(61 reference statements)

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“…Currently used as monotherapy, the inhibitor had only modest results. However, when combined with radiotherapy, the inhibitor induced radiosensitivity in 11 HGG cells [44]. This proved once again that HGG cells are able to develop resistance to therapies.…”

Section: Receptor Tyrosine Kinase Inhibitors For Glioblastoma Treatmentmentioning

confidence: 94%

Receptor tyrosine kinase targeting in glioblastoma: performance, limitations and future approaches

Alexandru¹,

Horescu²,

Sevastre³

et al. 2020

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From all central nervous system tumors, gliomas are the most common. Nowadays, researchers are looking for more efficient treatments for these tumors, as well as ways for early diagnosis. Receptor tyrosine kinases (RTKs) are major targets for oncology and the development of small-molecule RTK inhibitors has been proven successful in cancer treatment. Mutations or aberrant activation of the RTKs and their intracellular signaling pathways are linked to several malignant diseases, including glioblastoma. The progress in the understanding of malignant glioma evolution has led to RTK targeted therapies with high capacity to improve the therapeutic response while reducing toxicity. In this review, we present the most important RTKs (i.e. EGFR, IGFR, PDGFR and VEGFR) currently used for developing cancer therapeutics together with the potential of RTK-related drugs in glioblastoma treatment. Also, we focus on some therapeutic agents that are currently at different stages of research or even in clinical phases and proved to be suitable as re-purposing candidates for glioblastoma treatment.

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Section: Receptor Tyrosine Kinase Inhibitors For Glioblastoma Treatmentmentioning

confidence: 94%

Receptor tyrosine kinase targeting in glioblastoma: performance, limitations and future approaches

Alexandru¹,

Horescu²,

Sevastre³

et al. 2020

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“…In general, glioblastoma cells are resistant to chemotherapy and radiotherapy as well as to most apoptotic stimuli. However, there are many published papers showing sensitivity of glioma cells to certain small molecules in vitro .…”

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confidence: 99%

LAMP‐1 gene is overexpressed in high grade glioma

Sarafian

Koev²,

Mehterov

et al. 2018

APMIS

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High-grade gliomas (HGG) are the most frequent brain tumors in adults. Glioblastoma multiforme (GBM) is their most aggressive form resistant to therapy. It was shown that inhibition of autophagy reduced GBM development and autophagy interfering agents are regarded as a new strategy to fight glioma cells. The lysosome-associated membrane proteins (LAMPs) display differential expression particularly in cancer. There are few data on their expression and especially on their molecular profile. The aim of the present study is to investigate the expression of LAMP-1 and LAMP-2 genes and proteins in HGG. Newly diagnosed patients with HGG and healthy controls were examined by immunohistochemistry and qPCR for both protein and mRNA levels of LAMP-1 and LAMP-2. The transcriptional activity of LAMP-1 in HGG was significantly higher compared to normal brain and to LAMP-2. The two glycoproteins were detected in the cytosol of tumor cells with varying intensity, LAMP-1 showing again enhanced expression. In conclusion, novel data on LAMP-1 overexpression in HGG are presented suggesting involvement of this gene and protein in cell adhesion and tumor progression. These findings might help the elucidation of the complex biological role of the multifunctional LAMPs proteins and to predict novel therapeutic targets in lysosomes.

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“…The first and the most important is the presence of the blood brain barrier (BBB) which blocks the passage for over 90% of the agents used in the current clinical setting [16,17]. Secondly, GBMs have a propensity to quickly develop resistance to the therapeutic agents which penetrate the BBB, through multiple molecular pathways [18][19][20].…”

Section: Resultsmentioning

confidence: 99%

The Cytotoxic Effect of Rtks Inhibitors on Glioblastoma Cells. A Mathematical Model for Treatment Protocols Optimization

Brandusa¹,

Vatu²,

Purcaru³

et al. 2020

Rev. Chim.

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Medical oncology has seen an exponential growth in the last 20 years with the vast majority of malignancies receiving new therapeutic options with substantial benefits to patients� survival and quality of life. Glioblastomas (GBMs), however, have remained largely incurable, with over 90% of patients dying within 5 years of diagnosis. The estimation of a dose�effect type ratio, regarding the action of an oncological drug on tumor cells, leads to relevant conclusions in establishing the optimal medication, specific to the chemotherapeutic act. The identification of the optimal dose of agent is very important, based on experiments on cell lines with regards to cellular kinetics. In this study, we developed a mathematical model based on the specific transfer function of a dose�response action type of a drug on tumor cells in vitro.

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The Influence of EGFR Inactivation on the Radiation Response in High Grade Glioma

Cited by 17 publications

References 46 publications

Receptor tyrosine kinase targeting in glioblastoma: performance, limitations and future approaches

Receptor tyrosine kinase targeting in glioblastoma: performance, limitations and future approaches

LAMP‐1 gene is overexpressed in high grade glioma

The Cytotoxic Effect of Rtks Inhibitors on Glioblastoma Cells. A Mathematical Model for Treatment Protocols Optimization

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