Phase I trial of alisertib with concurrent fractionated stereotactic re-irradiation for recurrent high grade gliomas

Song, Andrew; Andrews, David W.; Werner‐Wasik, Maria; Kim, Lyndon; Glass, Jon; Bar‐Ad, Voichita; Evans, James J.; Farrell, Christopher; Judy, Kevin; Daskalakis, Constantine; Zhan, Tingting; Shi, Wenyin

doi:10.1016/j.radonc.2018.12.019

Cited by 26 publications

(14 citation statements)

References 35 publications

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“…In patient-derived orthotopic models of GBM resistant to bevacizumab, alisertib prolonged survival, induced mitotic arrest and decreased histone H3 phosphorylation (209). In a recent phase I clinical trial for GBM patients, alisertib was safe and well tolerated (210). Hence, although WNT signaling inhibitors show promising therapeutic rationale and results against GBM, the intricate crosstalk between EMT-autophagy-WNT needs further evaluation to gain a clearer understanding of how these processes and signaling pathways may be used against GBM.…”

Section: Crosstalk Between Autophagy Epithelial-mesenchymal Transitimentioning

confidence: 98%

Multifaceted WNT Signaling at the Crossroads Between Epithelial-Mesenchymal Transition and Autophagy in Glioblastoma

et al. 2020

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Section: Crosstalk Between Autophagy Epithelial-mesenchymal Transitimentioning

confidence: 98%

Multifaceted WNT Signaling at the Crossroads Between Epithelial-Mesenchymal Transition and Autophagy in Glioblastoma

et al. 2020

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“…Two other AURKA inhibitors, MLN8237 and ENMD-2076, also enhance radiation sensitivity in cancer cells [200,201]. A phase I trial on alisertib with fractionated stereotactic reirradiation therapy for patients with recurrent high-grade glioma has been conducted and has revealed that 40 mg of alisertib twice daily in combination with irradiation is safe and well tolerated [202]. Further exploration in the phase II trial may provide a better sense of clinical outcomes moving forward.…”

Section: Combination Therapymentioning

confidence: 99%

Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy

et al. 2021

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Aurora kinase A (AURKA) belongs to the family of serine/threonine kinases, whose activation is necessary for cell division processes via regulation of mitosis. AURKA shows significantly higher expression in cancer tissues than in normal control tissues for multiple tumor types according to the TCGA database. Activation of AURKA has been demonstrated to play an important role in a wide range of cancers, and numerous AURKA substrates have been identified. AURKA-mediated phosphorylation can regulate the functions of AURKA substrates, some of which are mitosis regulators, tumor suppressors or oncogenes. In addition, enrichment of AURKA-interacting proteins with KEGG pathway and GO analysis have demonstrated that these proteins are involved in classic oncogenic pathways. All of this evidence favors the idea of AURKA as a target for cancer therapy, and some small molecules targeting AURKA have been discovered. These AURKA inhibitors (AKIs) have been tested in preclinical studies, and some of them have been subjected to clinical trials as monotherapies or in combination with classic chemotherapy or other targeted therapies.

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“…Radiation from radiotherapy can adversely affect the patients' neurocognitive ability [152][153][154]. Hence, the application of fractionated radiotherapy or interstitial brachytherapy is thought to be safer and well-tolerated among HGG patients [155][156][157][158][159]. In a retrospective study, 59 recurrent GBM patients demonstrated prolonged median survival by eight months when given a median dose of 36 Gy radiotherapy with 2 Gy given each day [160].…”

Section: Challenges In Hgg Standard Therapymentioning

confidence: 99%

Challenges and Perspectives of Standard Therapy and Drug Development in High-Grade Gliomas

et al. 2021

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Despite their low incidence rate globally, high-grade gliomas (HGG) remain a fatal primary brain tumor. The recommended therapy often is incapable of resecting the tumor entirely and exclusively targeting the tumor leads to tumor recurrence and dismal prognosis. Additionally, many HGG patients are not well suited for standard therapy and instead, subjected to a palliative approach. HGG tumors are highly infiltrative and the complex tumor microenvironment as well as high tumor heterogeneity often poses the main challenges towards the standard treatment. Therefore, a one-fit-approach may not be suitable for HGG management. Thus, a multimodal approach of standard therapy with immunotherapy, nanomedicine, repurposing of older drugs, use of phytochemicals, and precision medicine may be more advantageous than a single treatment model. This multimodal approach considers the environmental and genetic factors which could affect the patient’s response to therapy, thus improving their outcome. This review discusses the current views and advances in potential HGG therapeutic approaches and, aims to bridge the existing knowledge gap that will assist in overcoming challenges in HGG.

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Phase I trial of alisertib with concurrent fractionated stereotactic re-irradiation for recurrent high grade gliomas

Cited by 26 publications

References 35 publications

Multifaceted WNT Signaling at the Crossroads Between Epithelial-Mesenchymal Transition and Autophagy in Glioblastoma

Multifaceted WNT Signaling at the Crossroads Between Epithelial-Mesenchymal Transition and Autophagy in Glioblastoma

Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy

Challenges and Perspectives of Standard Therapy and Drug Development in High-Grade Gliomas

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