Radioresistance in Glioblastoma and the Development of Radiosensitizers

Ali, Yousuf; Oliva, Claudia R.; Noman, Abu Shadat Mohammod; Allen, Bryan G.; Goswami, Prabhat C.; Zakharia, Yousef; Monga, Varun; Spitz, Douglas R.; Buatti, John M.; Griguer, Corinne E.

doi:10.3390/cancers12092511

Cited by 93 publications

(87 citation statements)

References 296 publications

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“…Residual masses and tumors that cannot be removed by surgery are commonly treated with high dose ionizing radiation (IR). However, radiotherapy tends to be ineffective, as GBMs are relatively radioresistant [33]. As previously anticipated, self-renewing and pluripotent GSCs might account for the observed radioresistance.…”

Section: Glioblastoma Therapiesmentioning

confidence: 79%

Zika Virus: A New Therapeutic Candidate for Glioblastoma Treatment

Francipane

Douradinha

Chinnici

et al. 2021

IJMS

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Glioblastoma (GBM) is the most aggressive among the neurological tumors. At present, no chemotherapy or radiotherapy regimen is associated with a positive long-term outcome. In the majority of cases, the tumor recurs within 32–36 weeks of initial treatment. The recent discovery that Zika virus (ZIKV) has an oncolytic action against GBM has brought hope for the development of new therapeutic approaches. ZIKV is an arbovirus of the Flaviviridae family, and its infection during development has been associated with central nervous system (CNS) malformations, including microcephaly, through the targeting of neural stem/progenitor cells (NSCs/NPCs). This finding has led various groups to evaluate ZIKV’s effects against glioblastoma stem cells (GSCs), supposedly responsible for GBM onset, progression, and therapy resistance. While preliminary data support ZIKV tropism toward GSCs, a more accurate study of ZIKV mechanisms of action is fundamental in order to launch ZIKV-based clinical trials for GBM patients.

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Section: Glioblastoma Therapiesmentioning

confidence: 79%

Zika Virus: A New Therapeutic Candidate for Glioblastoma Treatment

Francipane

Douradinha

Chinnici

et al. 2021

IJMS

View full text Add to dashboard Cite

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“…Radioresistance of GB GB tumors have been identified as therapy resistant due to multiple molecular mechanisms including inadequate drug blood-brain barrier (BBB) passage, intra-and intertumoral heterogeneity, redundant signaling pathways resulting in rescue mechanisms, adaptive radioresistance and an immunosuppressive tumor micro-environment (TME) promoted by a chronic state of hypoxia (15,(42)(43)(44). Hypoxic niches limiting the formation of reactive oxygen species (ROS) and a hyperactivation of the DNA damage response machinery induced by glioma stem cells (GSC) contribute to glioma radioresistance (44,45).…”

Section: Radiotherapy and Radioresistance Of Gbmentioning

confidence: 99%

MDM2/X Inhibitors as Radiosensitizers for Glioblastoma Targeted Therapy

et al. 2021

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Inhibition of the MDM2/X-p53 interaction is recognized as a potential anti-cancer strategy, including the treatment of glioblastoma (GB). In response to cellular stressors, such as DNA damage, the tumor suppression protein p53 is activated and responds by mediating cellular damage through DNA repair, cell cycle arrest and apoptosis. Hence, p53 activation plays a central role in cell survival and the effectiveness of cancer therapies. Alterations and reduced activity of p53 occur in 25-30% of primary GB tumors, but this number increases drastically to 60-70% in secondary GB. As a result, reactivating p53 is suggested as a treatment strategy, either by using targeted molecules to convert the mutant p53 back to its wild type form or by using MDM2 and MDMX (also known as MDM4) inhibitors. MDM2 down regulates p53 activity via ubiquitin-dependent degradation and is amplified or overexpressed in 14% of GB cases. Thus, suppression of MDM2 offers an opportunity for urgently needed new therapeutic interventions for GB. Numerous small molecule MDM2 inhibitors are currently undergoing clinical evaluation, either as monotherapy or in combination with chemotherapy and/or other targeted agents. In addition, considering the major role of both p53 and MDM2 in the downstream signaling response to radiation-induced DNA damage, the combination of MDM2 inhibitors with radiation may offer a valuable therapeutic radiosensitizing approach for GB therapy. This review covers the role of MDM2/X in cancer and more specifically in GB, followed by the rationale for the potential radiosensitizing effect of MDM2 inhibition. Finally, the current status of MDM2/X inhibition and p53 activation for the treatment of GB is given.

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“…A very interesting retrospective study conducted on patients with metastatic STSs using ICIs was conducted by Monga et al . [ 61 ]. Eighty-eight patients from 4 USA institutions with STSs, treated with a median of two previous therapies, received pembrolizumab (47 patients), nivolumab (6), ipilimumab (1), combination therapy ipilimumab and nivolumab (27).…”

Section: Immune Checkpoint Inhibitors (Icis)mentioning

confidence: 99%

Is immunotherapy in the future of therapeutic management of sarcomas?

et al. 2021

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Sarcomas are rare, ubiquitous and heterogeneous tumors usually treated with surgery, chemotherapy, target therapy, and radiotherapy. However, 25–50% of patients experience local relapses and/or distant metastases after chemotherapy with an overall survival about 12–18 months. Recently, immuno-therapy has revolutionized the cancer treatments with initial indications for non-small cell lung cancer (NSCLC) and melanoma (immune-checkpoint inhibitors).Here, we provide a narrative review on the topic as well as a critical description of the currently available trials on immunotherapy treatments in patients with sarcoma. Given the promising results obtained with anti-PD-1 monoclonal antibodies (pembrolizumab and nivolumab) and CAR-T cells, we strongly believe that these new immunotherapeutic approaches, along with an innovative characterization of tumor genetics, will provide an exciting opportunity to ameliorate the therapeutic management of sarcomas.

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Radioresistance in Glioblastoma and the Development of Radiosensitizers

Cited by 93 publications

References 296 publications

Zika Virus: A New Therapeutic Candidate for Glioblastoma Treatment

Zika Virus: A New Therapeutic Candidate for Glioblastoma Treatment

MDM2/X Inhibitors as Radiosensitizers for Glioblastoma Targeted Therapy

Is immunotherapy in the future of therapeutic management of sarcomas?

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