Enhancing glioblastoma treatment through the integration of tumor-treating fields

Szklener, Katarzyna; Bilski, Mateusz; Nieoczym, Karolina; Mańdziuk, Dominika; Mańdziuk, Sławomir

doi:10.3389/fonc.2023.1274587

Cited by 4 publications

(1 citation statement)

References 55 publications

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“…For instance, Crizotinib, an ALK inhibitor, has shown promise in combination with Temozolomide [74–76]. Panobinostat, a non-selective histone deacetylase inhibitor, enhances the effect of TMZ [77, 78] , while Lapatinib, a dual tyrosine kinase inhibitor of HER2 and EGFR pathways, has been tested in clinical trials for newly-diagnosed GBM [79] This approach aligns with the concept of combination therapy, aiming to target multiple molecular pathways simultaneously for a more comprehensive and effective treatment strategy [80–82] . Ultimately, this integrative analysis serves as a hypothesis-generating tool, proposing novel therapeutic combinations with the potential for improved efficacy in cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of drugs for repurposing in Glioblastoma: a computational and experimental workflow

Gonzalez,

Pérez Küper,

Garcia Fallit

et al. 2024

Preprint

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Purpose Glioblastoma (GBM) remains a formidable challenge in oncology due to its invasiveness and resistance to treatment, i.e. surgery, radiotherapy, and chemotherapy with temozolomide. This study aimed to develop and validate an integrated model to predict the sensitivity of GBM to alternative chemotherapeutics and to identify novel candidate drugs and combinations for the treatment of GBM. Methods We utilized the drug sensitivity response data of 272 compounds from CancerRxTissue, a validated predictive model, to identify drugs with therapeutic potential for GBM. Using the IC50, we selected 'potentially effective' drugs among those predicted to be blood-brain barrier permeable via in silico algorithms. We ultimately selected drugs with targets overexpressed and associated with worse prognosis in GBM for experimental in vitro validation. Results The workflow proposed predicted that GBM is more sensitive to Etoposide and Cisplatin, in comparison with Temozolomide, effects that were validated in vitro in a set of GBM cellular models. Using this workflow, we identified a set of 5 novel drugs to which GBM would exhibit high sensitivity and selected Daporinad, a blood-brain barrier permeant NAMPT inhibitor, for further preclinical in vitro evaluation, which aligned with the in silico prediction. Conclusion Our results suggest that this workflow could be useful to select potentially effective drugs and combinations for GBM, according to the molecular characteristics of the tumor. This comprehensive workflow, which integrates computational prowess with experimental validation, could constitute a simple tool for identifying and validating compounds with potential for drug repurposing in GBM and other tumors.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of drugs for repurposing in Glioblastoma: a computational and experimental workflow

Gonzalez,

Pérez Küper,

Garcia Fallit

et al. 2024

Preprint

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Efficacy and indications of gamma knife radiosurgery for recurrent low-and high-grade glioma

Sun,

Liu,

Wang

et al. 2024

BMC Cancer

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Purpose To investigate the indications and efficacy of gamma knife radiosurgery (GKRS) as a salvage treatment for recurrent low-and high-grade glioma. Methods This retrospective study of 107 patients with recurrent glioma treated with GKRS between 2009 and 2022, including 68 high-grade glioma (HGG) and 39 low-grade glioma (LGG) cases. The Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). The log-rank test was used to analyze the multivariate prognosis of the Cox proportional hazards model. Adverse reactions were evaluated according to the Common Terminology Criteria for Adverse Events version 4.03. The prognostic value of main clinical features was estimated, including histopathology, Karnofsky performance status (KPS), recurrence time interval, target location, two or more GKRS, surgery for recurrence, site of recurrence, left or right side of the brain and so on. Results The median follow-up time was 74.5 months. The median OS and PFS were 17.0 months and 5.5 months for all patients. The median OS and PFS were 11.0 months and 5.0 months for HGG, respectively. The median OS and PFS were 49.0 months and 12.0 months for LGG, respectively. Multivariate analysis showed that two or more GKRS, left or right side of the brain and brainstem significantly affected PFS. Meanwhile, the KPS index, two or more GKRS, pathological grade, and brainstem significantly affected OS. Stratified analysis showed that surgery for recurrence significantly affected OS and PFS for LGG. KPS significantly affected OS and PFS for HGG. No serious adverse events were noted post-GKRS. Conclusion GKRS is a safe and effective salvage treatment for recurrent glioma. Moreover, it can be applied after multiple recurrences with tolerable adverse effects.

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Integrating electromagnetic cancer stress with immunotherapy: a therapeutic paradigm

Fuster

2024

Front. Oncol.

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An array of published cell-based and small animal studies have demonstrated a variety of exposures of cancer cells or experimental carcinomas to electromagnetic (EM) wave platforms that are non-ionizing and non-thermal. Overall effects appear to be inhibitory, inducing cancer cell stress or death as well as inhibition in tumor growth in experimental models. A variety of physical input variables, including discrete frequencies, amplitudes, and exposure times, have been tested, but drawing methodologic rationale and mechanistic conclusions across studies is challenging. Nevertheless, outputs such as tumor cytotoxicity, apoptosis, tumor membrane electroporation and leak, and reactive oxygen species generation are intriguing. Early EM platforms in humans employ pulsed electric fields applied either externally or using interventional tumor contact to induce tumor cell electroporation with stromal, vascular, and immunologic sparing. It is also possible that direct or external exposures to non-thermal EM waves or pulsed magnetic fields may generate electromotive forces to engage with unique tumor cell properties, including tumor glycocalyx to induce carcinoma membrane disruption and stress, providing novel avenues to augment tumor antigen release, cross-presentation by tumor-resident immune cells, and anti-tumor immunity. Integration with existing checkpoint inhibitor strategies to boost immunotherapeutic effects in carcinomas may also emerge as a broadly effective strategy, but little has been considered or tested in this area. Unlike the use of chemo/radiation and/or targeted therapies in cancer, EM platforms may allow for the survival of tumor-associated immunologic cells, including naïve and sensitized anti-tumor T cells. Moreover, EM-induced cancer cell stress and apoptosis may potentiate endogenous tumor antigen-specific anti-tumor immunity. Clinical studies examining a few of these combined EM-platform approaches are in their infancy, and a greater thrust in research (including basic, clinical, and translational work) in understanding how EM platforms may integrate with immunotherapy will be critical in driving advances in cancer outcomes under this promising combination.

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Enhancing glioblastoma treatment through the integration of tumor-treating fields

Cited by 4 publications

References 55 publications

Identification and validation of drugs for repurposing in Glioblastoma: a computational and experimental workflow

Identification and validation of drugs for repurposing in Glioblastoma: a computational and experimental workflow

Efficacy and indications of gamma knife radiosurgery for recurrent low-and high-grade glioma

Integrating electromagnetic cancer stress with immunotherapy: a therapeutic paradigm

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