The Role of Hypoxia and SRC Tyrosine Kinase in Glioblastoma Invasiveness and Radioresistance

Torrisi, Filippo; Vicario, Nunzio; Spitale, Federica Maria; Cammarata, Francesco Paolo; Minafra, Luigi; Salvatorelli, Lucia; Russo, G.; Cuttone, G.; Valable, Samuel; Gulino, Rosario; Magro, Gaetano; Parenti, Rosalba

doi:10.3390/cancers12102860

Cited by 51 publications

(43 citation statements)

References 120 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For this reason, the tumor-treating field is considered as a standard of care in some guidelines [ 107 ]. Moreover, in the last years, the association of molecularly targeted drugs such as tyrosine kinase administration or others combined with X-rays to decrease radioresistance due to hypoxia showed encouraging results [ 108 , 109 , 110 ].…”

Section: Resultsmentioning

confidence: 99%

Diagnosis and Management of Glioblastoma: A Comprehensive Perspective

Gilard

Tebani

Dabaj

et al. 2021

JPM

View full text Add to dashboard Cite

Glioblastoma is the most common malignant brain tumor in adults. The current management relies on surgical resection and adjuvant radiotherapy and chemotherapy. Despite advances in our understanding of glioblastoma onset, we are still faced with an increased incidence, an altered quality of life and a poor prognosis, its relapse and a median overall survival of 15 months. For the past few years, the understanding of glioblastoma physiopathology has experienced an exponential acceleration and yielded significant insights and new treatments perspectives. In this review, through an original R-based literature analysis, we summarize the clinical presentation, current standards of care and outcomes in patients diagnosed with glioblastoma. We also present the recent advances and perspectives regarding pathophysiological bases as well as new therapeutic approaches such as cancer vaccination and personalized treatments.

show abstract

Section: Resultsmentioning

confidence: 99%

Diagnosis and Management of Glioblastoma: A Comprehensive Perspective

Gilard

Tebani

Dabaj

et al. 2021

JPM

View full text Add to dashboard Cite

show abstract

“…Indeed, IR is known to activate the transcription of genes, through the presence of cAMP-responsive elements (CREs) in their promoters, to guide cell fate and survival after radiation exposure [62][63][64]. Finally, it was reported that cancer-associated stress, including hypoxia, chronically activates the bioenergetic sensor AMP kinase (AMPK), as a pro-survival signal [65,66].…”

Section: Discussionmentioning

confidence: 99%

Hypoxia Transcriptomic Modifications Induced by Proton Irradiation in U87 Glioblastoma Multiforme Cell Line

Bravatà

Tinganelli

Cammarata

et al. 2021

JPM

Self Cite

View full text Add to dashboard Cite

In Glioblastoma Multiforme (GBM), hypoxia is associated with radioresistance and poor prognosis. Since standard GBM treatments are not always effective, new strategies are needed to overcome resistance to therapeutic treatments, including radiotherapy (RT). Our study aims to shed light on the biomarker network involved in a hypoxic (0.2% oxygen) GBM cell line that is radioresistant after proton therapy (PT). For cultivating cells in acute hypoxia, GSI’s hypoxic chambers were used. Cells were irradiated in the middle of a spread-out Bragg peak with increasing PT doses to verify the greater radioresistance in hypoxic conditions. Whole-genome cDNA microarray gene expression analyses were performed for samples treated with 2 and 10 Gy to highlight biological processes activated in GBM following PT in the hypoxic condition. We describe cell survival response and significant deregulated pathways responsible for the cell death/survival balance and gene signatures linked to the PT/hypoxia configurations assayed. Highlighting the molecular pathways involved in GBM resistance following hypoxia and ionizing radiation (IR), this work could suggest new molecular targets, allowing the development of targeted drugs to be suggested in association with PT.

show abstract

“…No clinical strategy has been approved by the FDA to reduce hypoxia in order to augment standard therapies. Many attempts have been made to increase oxygen delivery to tumors without clinical success [ 34 ]. These failures are partly due to limitations in tumor vessel function.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Regulation of Tumor Hypoxia in Model Murine Tumors and Spontaneous Canine Tumors

Benej

Kreamer

et al. 2021

Cancers

View full text Add to dashboard Cite

Background: Hypoxia is found in many solid tumors and is associated with increased disease aggressiveness and resistance to therapy. Reducing oxygen demand by targeting mitochondrial oxidative metabolism is an emerging concept in translational cancer research aimed at reducing hypoxia. We have shown that the U.S. Food and Drug Administration (FDA)-approved drug papaverine and its novel derivative SMV-32 are potent mitochondrial complex I inhibitors. Methods: We used a dynamic in vivo luciferase reporter system, pODD-Luc, to evaluate the impact of pharmacological manipulation of mitochondrial metabolism on the levels of tumor hypoxia in transplanted mouse tumors. We also imaged canine patients with blood oxygen level-dependent (BOLD) MRI at baseline and one hour after a dose of 1 or 2 mg/kg papaverine. Results: We showed that the pharmacological suppression of mitochondrial oxygen consumption (OCR) in tumor-bearing mice increases tumor oxygenation, while the stimulation of mitochondrial OCR decreases tumor oxygenation. In parallel experiments in a small series of spontaneous canine sarcomas treated at The Ohio State University (OSU) Veterinary Medical Center, we observed a significant increase in BOLD signals indicative of an increase in tumor oxygenation of up to 10–50 mm HgO2. Conclusion: In both transplanted murine tumors and spontaneous canine tumors we found that decreasing mitochondrial metabolism can decrease tumor hypoxia, potentially offering a therapeutic advantage.

show abstract

The Role of Hypoxia and SRC Tyrosine Kinase in Glioblastoma Invasiveness and Radioresistance

Cited by 51 publications

References 120 publications

Diagnosis and Management of Glioblastoma: A Comprehensive Perspective

Diagnosis and Management of Glioblastoma: A Comprehensive Perspective

Hypoxia Transcriptomic Modifications Induced by Proton Irradiation in U87 Glioblastoma Multiforme Cell Line

Pharmacological Regulation of Tumor Hypoxia in Model Murine Tumors and Spontaneous Canine Tumors

Contact Info

Product

Resources

About