Integrating electromagnetic cancer stress with immunotherapy: a therapeutic paradigm DOI Creative Commons
Mark M. Fuster

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Aug. 6, 2024

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

Language: Английский

Enhancing glioblastoma treatment through the integration of tumor-treating fields DOI Creative Commons
Katarzyna Szklener, Mateusz Bilski,

Karolina Nieoczym

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Oct. 17, 2023

Glioblastoma (GBM) represents a significant therapeutic challenge due to its aggressive nature. Tumor Treating Fields (TTFields) present promising approach GBM therapy. The primary mechanism of TTFields, an antimitotic effect, alongside numerous indirect effects including increased cell membrane permeability, signifies their potential in combination with other treatment modalities. Current combinations often include chemotherapy, particularly temozolomide (TMZ), however, emerging data suggests synergy targeted therapies, radiotherapy, and immunotherapy as well. TTFields display minimal side effects, predominantly skin-related, posing no barrier combined therapies. effectiveness has been demonstrated through several post-registration studies, advocating for continued research optimize overall survival (OS) progression-free (PFS) patients, opposed focusing solely on quality life.

Language: Английский

Citations

12
Therapeutic potential of tumor treating fields for malignant brain tumors DOI Creative Commons
Youyou Zhou,

Xiaoqing Xing,

Jinyun Zhou

et al.

Cancer Reports, Journal Year: 2023, Volume and Issue: 6(5)

Published: March 29, 2023

Abstract Background Malignant brain tumors are among the most threatening diseases of central nervous system, and despite increasingly updated treatments, prognosis has not been improved. Tumor treating fields (TTFields) an emerging approach in cancer treatment using intermediate‐frequency low‐intensity electric field can lead to development novel therapeutic options. Recent Findings A series biological processes induced by TTFields exert anti‐cancer effects have identified. studies shown that alter bioelectrical state macromolecules organelles involved biology. Massive alterations cell proteomics transcriptomics caused were related as well multiple organelle structures activities. This review addresses mechanisms recent advances application therapy malignant tumors, especially glioblastoma (GBM). Conclusions As a strategy, promising results many clinical trials, GBM, continue evolve. growing number patients with being enrolled ongoing demonstrating TTFields‐based combination therapies improve outcomes.

Language: Английский

Citations

11
Association of tumor treating fields (TTFields) therapy with overall survival in newly diagnosed glioblastoma DOI
Siddharth Shah, Aiswarya Nag, Brandon Lucke‐Wold

et al.

Clinical & Translational Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Tumor Treating Fields and Combination Therapy in Management of Brain Oncology DOI Open Access
Ruilin Liu,

James H. Huang,

Xiaoming Qi

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(7), P. 1211 - 1211

Published: April 2, 2025

Glioblastoma (GBM) remains a challenging cancer to treat with limited effective therapies. Standard treatments, including surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, offer marginal survival benefits but are often by side effects drug resistance. Temozolomide is the most commonly used chemotherapy; however, resistance lack of efficacy in recurrent GBM hinder its success. Tumor treating fields (TTFields), novel non-invasive modality that utilizes alternating electric fields, have recently emerged as promising treatment for GBM. TTFields work disrupting function mitotic spindle inducing apoptosis cells. They can be especially when combined other enhance delivery paired chemotherapy increasing permeability blood-brain barrier cell membranes, leading more tumor inhibition. Similarly, increase sensitivity radiation therapy improve therapies, such sorafenib particularly extra-cranial tumors. The Optune device, primary medical device TTFields' delivery, offers convenient versatile option, allowing remote care exhibiting fewer adverse effects. This review discusses potential valuable addition treatment, combination highlights device's clinical applications.

Language: Английский

Citations

0
Synthesis of selective BCL-XL PROTAC and potent antitumor activity in glioblastoma DOI Creative Commons
Meichen Liu, Biao Sun, Rui Niu

et al.

Cell Reports Physical Science, Journal Year: 2025, Volume and Issue: unknown, P. 102593 - 102593

Published: May 1, 2025

Language: Английский

Citations

0
Synthesis of selective BCL-XL PROTAC and potent antitumor activity in glioblastoma DOI Creative Commons
Jinlong Yin, Biao Sun, Meichen Liu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 19, 2024

Abstract Glioblastoma (GBM), the most aggressive and treatment-resistant form of brain cancer, is significantly influenced by GBM stem cells (GSCs), which contribute to tumor initiation recurrence. In this study, we introduce two novel proteolysis-targeting chimeras (PROTACs), AN-1 AN-2, engineered degrade BCL-XL, a critical anti-apoptotic protein in BCL-2 family. These PROTACs are optimized from ABT-263 uniquely utilize MDM2 as an E3 ligase, strategy not previously employed therapy. Our approach leverages high expression GSCs versus its low platelets, enhancing therapeutic specificity reducing risk thrombocytopenia—a major side effect direct BCL-XL inhibition. Both vitro in vivo studies demonstrate that AN-2 effectively inhibit GSC proliferation, promote apoptosis, substantially improve survival rates without inducing thrombocytopenia. This work only highlights potential targeting underutilized ligases for cancer therapy but also suggests highly selective treating might overcome current limitations existing therapies.

Language: Английский

Citations

1
Prediction of intracranial electric field strength and analysis of treatment protocols in tumor electric field therapy targeting gliomas of the brain DOI

Jun Wen,

Liling Xiong,

Shulu Wang

et al.

Computer Methods and Programs in Biomedicine, Journal Year: 2024, Volume and Issue: 258, P. 108490 - 108490

Published: Nov. 2, 2024

Language: Английский

Citations

0
Prospects of earthworm coelomic fluid as a potential therapeutic agent to treat cancer DOI
Shafiul Haque, Arif Hussain, Atiah H. Almalki

et al.

Cancer and Metastasis Reviews, Journal Year: 2023, Volume and Issue: 43(2), P. 621 - 637

Published: Nov. 1, 2023

Language: Английский

Citations

1
A Scoping Review of Focused Ultrasound Enhanced Drug Delivery for Across the Blood–Brain Barrier for Brain Tumors DOI

Christopher M. Young,

Ariel Viña-González,

Rodrigo Salmeron de Toledo Aguiar

et al.

Operative Neurosurgery, Journal Year: 2024, Volume and Issue: 27(5), P. 523 - 532

Published: May 8, 2024

BACKGROUND AND OBJECTIVES: Previous mechanisms of opening the blood–brain barrier (BBB) created a hypertonic environment. Focused ultrasound (FUS) has recently been introduced as means controlled BBB opening. Here, we performed scoping review to assess advances in drug delivery across for treatment brain tumors identify and literature gaps. METHODS: A current was conducted through MEDLINE search inclusive articles on FUS, BBB, tumor barrier, including human, modeling, animal studies written English. Using Rayyan platform, 2 reviewers (J.P C.Y) identified 967 publications. 224 were chosen after title screen. Ultimately 98 reviewed. The designed address following questions: (1) What FUS technology improvements have made augment tumors? (2) occurred ensure better uptake target tissue RESULTS: Microbubbles (MB) with are used (BBBO) cavitation increase its permeability. Drug into central nervous system can be combined MB enhance transport therapeutic agents resulting suppression growth prolonging survival rate, well reducing systemic toxicity degradation rate. There is accumulating evidence demonstrating that BBBO FUS-MB improves concentrations provides impact rates, compared drug-only treatments. CONCLUSION: role BBBO. Identified gaps include microenvironment extracellular space, improved understanding control delivery, further work ideal pharmacologics clinical use.

Language: Английский

Citations

0
Directionally non-rotating electric field therapy delivered through implanted electrodes as a glioblastoma treatment platform: A proof-of-principle study DOI Creative Commons
Jun Ma, Shilpi Singh, Ming Li

et al.

Neuro-Oncology Advances, Journal Year: 2024, Volume and Issue: 6(1)

Published: Jan. 1, 2024

Abstract Background While directionally rotating tumor-treating fields (TTF) therapy has garnered considerable clinical interest in recent years, there been comparatively less focus on non-rotating electric field (dnEFT). Methods We explored dnEFT generated through customized electrodes as a glioblastoma vitro and vivo preclinical models. The effects of tumor apoptosis microglia/macrophages the microenvironment were tested using flow-cytometric qPCR assays. Results In vitro, clinical-grade spinal cord stimulator showed antineoplastic activity against independent cell lines. support results obtained electrode, delivered customized, 2-electrode array induced apoptosis. To characterize this effect vivo, custom-designed 4-electrode was fabricated such that cells can be implanted into murine cerebrum center channel equidistant from electrodes. After implantation with luciferase-expressing GL261 cells, mice randomized to or placebo. Relative placebo-treated mice, reduced growth (measured by bioluminescence) prolonged survival (median gain 6.5 days). Analysis brain sections following notable increase accumulation peritumoral macrophage/microglia increased expression M1 genes (IFNγ, TNFα, IL-6) decreased M2 (CD206, Arg, IL-10) relative tumors. Conclusions Our suggest therapeutic potential for electrodes, supporting development proof-of-principle trial commercially available deep

Language: Английский

Citations

0