Entrectinib demonstrates prolonged efficacy in an adult case of radiation-refractory <i>NTRK</i> fusion glioblastoma

Grogan, Patrick T.; Deming, Dustin A.; Helgager, Jeffrey; Ruszkiewicz, Theresa; Başkaya, Mustafa K.; Howard, Steven; Robins, H. Ian

doi:10.1093/noajnl/vdac046

Cited by 4 publications

(3 citation statements)

References 18 publications

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“…The role of repotrectinib (NCT04094610), like the role of larotrectinib (NCT02637687, NCT02576431) is being studied in phase I/II trials at the moment. Entrectinib, an NTRK/ROS1 (c-ros oncogene 1)/ALK (anaplastic lymphoma kinase) pathway inhibitor, was tested, with promising results, in a case of a radiation recurrent GB [99].…”

Section: Ntrk Inhibitorsmentioning

confidence: 99%

Overcoming Resistance to Temozolomide in Glioblastoma: A Scoping Review of Preclinical and Clinical Data

Smerdi,

Moutafi,

Kotsantis

et al. 2024

Life

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Glioblastoma (GB) is the most common and most aggressive primary brain tumor in adults, with an overall survival almost 14.6 months. Optimal resection followed by combined temozolomide chemotherapy and radiotherapy, also known as Stupp protocol, remains the standard of treatment; nevertheless, resistance to temozolomide, which can be obtained throughout many molecular pathways, is still an unsurpassed obstacle. Several factors influence the efficacy of temozolomide, including the involvement of other DNA repair systems, aberrant signaling pathways, autophagy, epigenetic modifications, microRNAs, and extracellular vesicle production. The blood–brain barrier, which serves as both a physical and biochemical obstacle, the tumor microenvironment’s pro-cancerogenic and immunosuppressive nature, and tumor-specific characteristics such as volume and antigen expression, are the subject of ongoing investigation. In this review, preclinical and clinical data about temozolomide resistance acquisition and possible ways to overcome chemoresistance, or to treat gliomas without restoration of chemosensitinity, are evaluated and presented. The objective is to offer a thorough examination of the clinically significant molecular mechanisms and their intricate interrelationships, with the aim of enhancing understanding to combat resistance to TMZ more effectively.

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Section: Ntrk Inhibitorsmentioning

confidence: 99%

Overcoming Resistance to Temozolomide in Glioblastoma: A Scoping Review of Preclinical and Clinical Data

Smerdi,

Moutafi,

Kotsantis

et al. 2024

Life

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“… 35 Mostly, they also include patients in the relapse setting and primarily consider the overall response rate, which, as previously discussed, is challenging for glioblastoma. 32 , 36 , 37 In conclusion, although encouraging results with neurotrophic tyrosine receptor kinase (NTRK) gene fusions and BRAF V600E mutations have come from basket trials, they lack the necessary design capabilities to assess targeted therapies for glioblastoma efficiently. 36 , 38 In contrast, platform trials allow the previously discussed features such as biomarker enrichment, common control arms, and testing experimental agents in the first line and have gained popularity in the glioblastoma trial landscape.…”

Section: Prudent Trial Designsmentioning

confidence: 99%

“…NTRK gene fusions and fibroblast growth factor receptor 3 and acidic coiled-coil 3 (FGFR3-TACC3) fusions have shown to be druggable and larger biomarker-driven trials are now ongoing—NCT04142437, NCT02568267, and NCT05267106. 37 , 38 , 67 , 68 Other oncogenic fusions, such as EGFR fusions, FIG-ROS fusions, and non-coding RNA, also hold the potential of becoming future targets. 65 …”

Section: Considered Drug and Target Selectionmentioning

confidence: 99%

Implementing targeted therapies in the treatment of glioblastoma: Previous shortcomings, future promises, and a multimodal strategy recommendation

Fougner

Hasselbalch

Lassen

et al. 2022

Neuro-Oncology Advances

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The introduction of targeted therapies to the field of oncology has prolonged the survival in several tumor types. Despite extensive research and numerous trials, similar outcomes have unfortunately not been realized for glioblastoma. For more than 15 years, the standard treatment of glioblastoma has been unchanged. This review walks through the elements that have challenged the success of previous trials and highlight some future promises. Concurrently, this review describes how institutions, through a multimodal and comprehensive strategy with four essential components, may increase the probability of finding a meaningful role for targeted therapies in the treatment of glioblastoma. These components are (1) prudent trial designs, (2) considered drug and target selection, (3) harnessed real-world clinical and molecular evidence, and (4) incorporation of translational research.

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RNA fusion transcript panel identifies diverse repertoire of fusions in adult glioma patients with therapeutic implications

Kothari

Dusenbery

Doucette

et al. 2023

Neuro-Oncology Practice

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Background Recurrent gliomas are therapeutically challenging diseases with few treatment options available. One area of potential therapeutic vulnerability is the presence of targetable oncogenic fusion proteins. Methods To better understand the clinical benefit of routinely testing for fusion proteins in adult glioma patients, we performed a retrospective review of 647 adult patients with glioma who underwent surgical resection at our center between August 2017-May 2021 and whose tumors were analyzed with an in-house fusion transcript panel (FTP). Results Fifty-two patients (8%) were found to harbor a potentially targetable fusion with eleven (21%) of these patients receiving treatment with a fusion targeted inhibitor. The targetable genes found to be involved in a fusion included FGFR3, MET, EGFR, NTRK1, NTRK2, BRAF, ROS1, and PIK3CA. Conclusions This analysis demonstrates that routine clinical testing for gene fusions identifies a diverse repertoire of potential therapeutic targets in adult patients with glioma and can offer rational therapeutic options for patients with recurrent disease.

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Entrectinib demonstrates prolonged efficacy in an adult case of radiation-refractory NTRK fusion glioblastoma

Cited by 4 publications

References 18 publications

Overcoming Resistance to Temozolomide in Glioblastoma: A Scoping Review of Preclinical and Clinical Data

Overcoming Resistance to Temozolomide in Glioblastoma: A Scoping Review of Preclinical and Clinical Data

Implementing targeted therapies in the treatment of glioblastoma: Previous shortcomings, future promises, and a multimodal strategy recommendation

RNA fusion transcript panel identifies diverse repertoire of fusions in adult glioma patients with therapeutic implications

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