The transcriptomic fingerprint of cancer response to Tumor Treating Fields (TTFields)
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PROVIDER: PRJEB87601 | ENA |
REPOSITORIES: ENA
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Project description:Tumor Treating Fields (TTFields) disturbs mitosis and consequently leads to cell cycle arrest and cell death. Mild hyperthermia induces cancer cell death by apoptosis,leading to DNA damage and disturbing DNA repair. Thus, when mild hyperthermia is combined with TTFields, the anti-tumor effect could be augmented. This prompted the hypothesis for the present thesis: TTFields and mild hyperthermia as synergistic modalities in Pancreatic ductal adenocarcinoma (PDAC) treatment could probably enhance antitumor efficacy and abate individual toxic effects through distinct and overlapping mechanisms target the tumor cell. Our established PDAC cell line (Bx-GEM) was treated with TTFields and TTFields with mild hyperthermia and was examined by microarray. 500 ng mRNA was checked for quality control and the concentration was measured again. Subsequently, gene expression profiling was performed using human HuGene-2_0-st-type array from Affymetrix.
2021-03-17 | E-MTAB-10270 | biostudies-arrayexpress
Project description:We used 3 established GBM cell lines to generate TTFields-resistant cells using Inovitro system.
2024-10-08 | GSE270513 | GEO
Project description:We report the application of RNA-based sequencing technology for high-throughput profiling of T cell enriched peripheral blood mononuclear cells. By sequencing in total of 12 pairs GBM patient samples, we extracted TCRαβ V(D)J sequences from the deep RNA-seq of T cells isolated from the 24 PBMCs to determine if TTFields treatment affected TCR diversity, using the Simpson’s diversity index (DI), which is the average proportional abundance of TCR clones based on the weighted arithmetic mean. Of the 12 patients, 9 exhibited negative log fold change (logFC) of TCR DI after TTFields, indicating clonal expansion. Notably, in all but 1 patient, the top 200 most abundant clones post TTFields, which accounted for 38.1% to 100% (median 67%) of detectable clones, showed substantial expansion compared to pre-TTFields T cells, and inversely correlated with the DI. Thus, TTFields treatment is associated with adaptive immune activation as evidenced by clonal expansion of peripheral T cells.
2022-04-20 | GSE193729 | GEO
Project description:Despite improved survival outcomes across many cancer types, the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic cancer. Invariably in these cancers, the control achieved by time-limited interventions such as traditional surgical resection, radiation therapy, and chemotherapy is short-lived. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outcomes in patients. Although the pre-clinical and clinical data are promising, the mechanisms of TTFields are not fully elucidated. Many investigations are underway to better understand how and why TTFields is able to selectively kill cancer cells and impede their proliferation. The purpose of this review is to summarize and discuss the reported mechanisms of action of TTFields from pre-clinical studies (both in vitro and in vivo). An improved understanding of how TTFields works will guide strategies focused on the timing and combination of TTFields with other therapies, to further improve survival outcomes in patients with solid organ cancers.
| S-EPMC9912101 | biostudies-literature
Project description:TTFields Glioblastoma
| PRJEB56095 | ENA
Project description:Transcriptomic analysis of glioblastoma (GBM) patients’ samples before and after treatment either with standard chemoradiation (TMZ+RT) or chemoradiation + TTFields (Novocure) 200 kHz. The original study (Diamant et al J Immunol 2021) evaluated changes in immune signature and immune infiltrate as evaluated by immune cell signatures.
| EGAS00001005392 | EGA
Project description:PurposeMesenchymal stromal cells (MSCs) within the glioblastoma microenvironment have been shown to promote tumor progression. Tumor Treating Fields (TTFields) are alternating electric fields with low intensity and intermediate frequency that exhibit anti-tumorigenic effects. While the effects of TTFields on glioblastoma cells have been studied previously, nothing is known about the influence of TTFields on MSCs.MethodsSingle-cell RNA sequencing and immunofluorescence staining were employed to identify glioblastoma-associated MSCs in patient samples. Proliferation and clonogenic survival of human bone marrow-derived MSCs were assessed after TTFields in vitro. MSC' characteristic surface marker expression was determined using flow cytometry, while multi-lineage differentiation potential was examined with immunohistochemistry. Apoptosis was quantified based on caspase-3 and annexin-V/7-AAD levels in flow cytometry, and senescence was assessed with ß-galactosidase staining. MSCs' migratory potential was evaluated with Boyden chamber assays.ResultsSingle-cell RNA sequencing and immunofluorescence showed the presence of glioblastoma-associated MSCs in patient samples. TTFields significantly reduced proliferation and clonogenic survival of human bone marrow-derived MSCs by up to 60% and 90%, respectively. While the characteristic surface marker expression and differentiation capacity were intact after TTFields, treatment resulted in increased apoptosis and senescence. Furthermore, TTFields significantly reduced MSCs' migratory capacity.ConclusionWe could demonstrate the presence of tumor-associated MSCs in glioblastoma patients, providing a rationale to study the impact of TTFields on MSCs. TTFields considerably increase apoptosis and senescence in MSCs, resulting in impaired survival and migration. The results provide a basis for further analyses on the role of MSCs in glioblastoma patients receiving TTFields.
| S-EPMC11341748 | biostudies-literature
Project description:Non-small cell lung cancer, ovarian cancer, and pancreatic cancer all present with high morbidity and mortality. Systemic chemotherapies have historically been the cornerstone of standard of care (SOC) regimens for many cancers, but are associated with systemic toxicity. Multimodal treatment combinations can help improve patient outcomes; however, implementation is limited by additive toxicities and potential drug-drug interactions. As such, there is a high unmet need to develop additional therapies to enhance the efficacy of SOC treatments without increasing toxicity. Tumor Treating Fields (TTFields) are electric fields that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. The therapy is locoregional and is delivered noninvasively to the tumor site via a portable medical device that consists of field generator and arrays that are placed on the patient's skin. As a noninvasive treatment modality, TTFields therapy-related adverse events mainly consist of localized skin reactions, which are manageable with effective acute and prophylactic treatments. TTFields selectively target cancer cells through a multi-mechanistic approach without affecting healthy cells and tissues. Therefore, the application of TTFields therapy concomitant with other cancer treatments may lead to enhanced efficacy, with low risk of further systemic toxicity. In this review, we explore TTFields therapy concomitant with taxanes in both preclinical and clinical settings. The summarized data suggest that TTFields therapy concomitant with taxanes may be beneficial in the treatment of certain cancers.
| S-EPMC9913762 | biostudies-literature
Project description:BackgroundTumor Treating Fields (TTFields), are a novel, non-invasive tissue ablation technology for treatment of cancer. Tissue ablation is achieved through the continuous delivery of a narrow range of electromagnetic fields across a tumor, for a period of months. TTFields are designed to affect only cells that divide and to interfere with the cell division process. The therapy is monitored with MRI imaging, performed every couple of months. Current technology is unable to assess the treatment effectiveness in real time.MethodsWe propose that the effect of the treatment can be assessed, in real time, by continuously measuring the change in electrical impedance across the TTFields delivery electrode arrays. An in vitro anatomic skull experimental study, with brain and tumor mimics phantom tissues was conducted to confirm the potential value of the proposed monitoring system.ResultsExperiments show that measuring the change in the impedance amplitude between opposite TTFields electrode arrays, at a typical TTFields treatment frequency of (200 kHz), can detect changes in the tumor radius with a sensitivity that increases with the radius of the tumor. The study shows that TTFields electrode arrays can be used to assess the effectiveness of TTFields treatment on changes in the tumor dimensions in real time, throughout the treatement. This monitoring system may become a valuable addition to the TTFields cancer treatment technology. It could provide the means to continuously assess the effectiveness of the treatment, and thereby optimize the design of the treatment protocol.
| S-EPMC8833244 | biostudies-literature
Project description:PurposeThis study investigates the biological effect of Tumor Treating Fields (TTFields) on key drivers of glioblastoma's malignancy-tumor microtube (TM) formation-and on the function and overall integrity of the tumor cell network.MethodUsing a two-dimensional monoculture GB cell network model (2DTM) of primary glioblastoma cell (GBC) cultures (S24, BG5 or T269), we evaluated the effects of TTFields on cell density, interconnectivity and structural integrity of the tumor network. We also analyzed calcium (Ca2+) transient dynamics and network morphology, validating findings in patient-derived tumoroids and brain tumor organoids.ResultsIn the 2DTM assay, TTFields reduced cell density by 85-88% and disrupted network interconnectivity, particularly in cells with multiple TMs. A "crooked TM" phenotype emerged in 5-6% of treated cells, rarely seen in controls. Ca2+ transients were significantly compromised, with global Ca2+ activity reduced by 51-83%, active and periodic cells by over 50%, and intercellular co-activity by 52% in S24, and almost completely in BG5 GBCs. The effects were more pronounced at 200 kHz compared to a 50 kHz TTFields. Similar reductions in Ca2+ activity were observed in patient-derived tumoroids. In brain tumor organoids, TTFields significantly reduced tumor cell proliferation and infiltration.ConclusionOur comprehensive study provides new insights into the multiple effects of Inovitro-modeled TTFields on glioma progression, morphology and network dynamics in vitro. Future in vivo studies to verify our in vitro findings may provide the basis for a deeper understanding and optimization of TTFields as a therapeutic modality in the treatment of GB.
| S-EPMC11457690 | biostudies-literature