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Article: Development and Optimisation of Tumour Treating Fields (TTFields) Delivery within 3D Primary Glioma Stem Cell-like Models of Spatial Heterogeneity.

Jones, Callum G / Vanderlinden, Aurelie / Rominiyi, Ola / Collis, Spencer J

2024 Volume 16, Issue 5

Abstract: Glioblastoma is an aggressive, incurable brain cancer with poor five-year survival rates of around 13% despite multimodal treatment with surgery, DNA-damaging chemoradiotherapy and the recent addition of Tumour Treating Fields (TTFields). As such, there ... ...

Abstract	Glioblastoma is an aggressive, incurable brain cancer with poor five-year survival rates of around 13% despite multimodal treatment with surgery, DNA-damaging chemoradiotherapy and the recent addition of Tumour Treating Fields (TTFields). As such, there is an urgent need to improve our current understanding of cellular responses to TTFields using more clinically and surgically relevant models, which reflect the profound spatial heterogeneity within glioblastoma, and leverage these biological insights to inform the rational design of more effective therapeutic strategies incorporating TTFields. We have recently reported the use of preclinical TTFields using the inovitro
Language	English
Publishing date	2024-02-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16050863
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Article ; Online: DDRugging glioblastoma: understanding and targeting the DNA damage response to improve future therapies.

Rominiyi, Ola / Collis, Spencer J

Molecular oncology

2021 Volume 16, Issue 1, Page(s) 11–41

Abstract: Glioblastoma is the most frequently diagnosed type of primary brain tumour in adults. These aggressive tumours are characterised by inherent treatment resistance and disease progression, contributing to ~ 190 000 brain tumour-related deaths globally each ...

Abstract	Glioblastoma is the most frequently diagnosed type of primary brain tumour in adults. These aggressive tumours are characterised by inherent treatment resistance and disease progression, contributing to ~ 190 000 brain tumour-related deaths globally each year. Current therapeutic interventions consist of surgical resection followed by radiotherapy and temozolomide chemotherapy, but average survival is typically around 1 year, with < 10% of patients surviving more than 5 years. Recently, a fourth treatment modality of intermediate-frequency low-intensity electric fields [called tumour-treating fields (TTFields)] was clinically approved for glioblastoma in some countries after it was found to increase median overall survival rates by ~ 5 months in a phase III randomised clinical trial. However, beyond these treatments, attempts to establish more effective therapies have yielded little improvement in survival for patients over the last 50 years. This is in contrast to many other types of cancer and highlights glioblastoma as a recognised tumour of unmet clinical need. Previous work has revealed that glioblastomas contain stem cell-like subpopulations that exhibit heightened expression of DNA damage response (DDR) factors, contributing to therapy resistance and disease relapse. Given that radiotherapy, chemotherapy and TTFields-based therapies all impact DDR mechanisms, this Review will focus on our current knowledge of the role of the DDR in glioblastoma biology and treatment. We also discuss the potential of effective multimodal targeting of the DDR combined with standard-of-care therapies, as well as emerging therapeutic targets, in providing much-needed improvements in survival rates for patients.
MeSH term(s)	Adult ; Brain Neoplasms/drug therapy ; Brain Neoplasms/therapy ; Clinical Trials, Phase III as Topic ; Combined Modality Therapy ; DNA Damage ; Glioblastoma/drug therapy ; Glioblastoma/therapy ; Humans ; Randomized Controlled Trials as Topic ; Temozolomide/pharmacology ; Temozolomide/therapeutic use
Chemical Substances	Temozolomide (YF1K15M17Y)
Language	English
Publishing date	2021-06-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2415106-3
ISSN	1878-0261 ; 1574-7891
ISSN (online)	1878-0261
ISSN	1574-7891
DOI	10.1002/1878-0261.13020
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Article: Development of a wind turbine for a hybrid solar-wind power system.

Adetunla, Adedotun / Rominiyi, Oluwasina / Adaramola, Bernard / Adeoye, Adeyinka

Heliyon

2022 Volume 8, Issue 11, Page(s) e11458

Abstract: Conventional energy supply has not been able to meet the energy needs of most developing nations. This calls for the need to invest in renewable energy systems which are not only sustainable but clean, abundant, and easily assessable. This research ... ...

Abstract	Conventional energy supply has not been able to meet the energy needs of most developing nations. This calls for the need to invest in renewable energy systems which are not only sustainable but clean, abundant, and easily assessable. This research presents a study of wind variability by using wind data got from a weather station to design and fabricate a small-scale horizontal axis wind turbine (HAWT). This was done by using locally sourced materials for a Hybrid Solar-Wind power system for irrigation purposes, as a performance evaluation of the turbine. The materials used in the fabrication of the turbine include wood, polyvinyl chloride plastic, acrylic glass, Teflon, and steel all sourced locally. From the evaluation, the power capacity of the wind turbine was derived to be 40 W, 41 W and 43 W from the voltage and current output reading on the multi-meter from three average wind speed variations of 5 m/s, 10 m/s and 15 m/s measured from handheld digital anemometers respectively. A regression analysis of the relationship between the turbine's power capacity and the wind speed showed that the turbine operates best at low speed of 5 m/s, with an R
Language	English
Publishing date	2022-11-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2022.e11458
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Article ; Online: DNA damage response inhibitors enhance tumour treating fields (TTFields) potency in glioma stem-like cells.

Vanderlinden, Aurelie / Jones, Callum G / Myers, Katie N / Rominiyi, Ola / Collis, Spencer J

British journal of cancer

2023 Volume 129, Issue 11, Page(s) 1829–1840

Abstract: Background: High-grade gliomas are primary brain cancers with unacceptably low and persistent survival rates of 10-16 months for WHO grade 4 gliomas over the last 40 years, despite surgical resection and DNA-damaging chemo-radiotherapy. More recently, ... ...

Abstract	Background: High-grade gliomas are primary brain cancers with unacceptably low and persistent survival rates of 10-16 months for WHO grade 4 gliomas over the last 40 years, despite surgical resection and DNA-damaging chemo-radiotherapy. More recently, tumour-treating fields therapy (TTFields) has demonstrated modest survival benefit and been clinically approved in several countries. TTFields is thought to mediate anti-cancer activity by primarily disrupting mitosis. However, recent data suggest that TTFields may also attenuate DNA damage repair and replication fork dynamics, providing a potential platform for therapeutic combinations incorporating standard-of-care treatments and targeted DNA damage response inhibitors (DDRi). Methods: We have used patient-derived, typically resistant, glioma stem-like cells (GSCs) in combination with the previously validated preclinical Inovitro™ TTFields system together with a number of therapeutic DDRi. Results: We show that TTFields robustly activates PARP- and ATR-mediated DNA repair (including PARylation and CHK1 phosphorylation, respectively), whilst combining TTFields with PARP1 or ATR inhibitor treatment leads to significantly reduced clonogenic survival. The potency of each of these strategies is further enhanced by radiation treatment, leading to increased amounts of DNA damage with profound delay in DNA damage resolution. Conclusion: To our knowledge, our findings represent the first report of TTFields applied with clinically approved or in-trial DDRi in GSC models and provides a basis for translational studies toward multimodal DDRi/TTFields-based therapeutic strategies for patients with these currently incurable tumours.
MeSH term(s)	Humans ; Glioma/pathology ; DNA Repair ; DNA Damage ; Mitosis
Language	English
Publishing date	2023-09-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-023-02454-0
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Article: The 'Ins and Outs' of Early Preclinical Models for Brain Tumor Research: Are They Valuable and Have We Been Doing It Wrong?

Rominiyi, Ola / Al-Tamimi, Yahia / Collis, Spencer J

Cancers

2019 Volume 11, Issue 3

Abstract: In this perspective, we congratulate the international efforts to highlight critical challenges in brain tumor research through a recent Consensus Statement. We also illustrate the importance of developing more accurate and clinically relevant early ... ...

Abstract	In this perspective, we congratulate the international efforts to highlight critical challenges in brain tumor research through a recent Consensus Statement. We also illustrate the importance of developing more accurate and clinically relevant early translational in vitro brain tumor models-a perspective given limited emphasis in the Consensus Statement, despite in vitro models being widely used to prioritize candidate therapeutic strategies prior to in vivo studies and subsequent clinical trials. We argue that successful translation of effective novel treatments into the clinic will require investment into the development of more predictive early pre-clinical models. It is in the interest of researchers, clinicians, and ultimately, patients that the most promising therapeutic candidates are identified and translated toward use in the clinic. Highlighting the value of early pre-clinical brain tumor models and debating how such models can be improved is of the utmost importance to the neuro-oncology research community and cancer research more broadly.
Language	English
Publishing date	2019-03-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers11030426
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Article ; Online: Is cranial computed tomography unnecessary in children with a head injury and isolated vomiting?

Hardman, Simon / Rominiyi, Ola / King, David / Snelson, Edward

BMJ (Clinical research ed.)

2019 Volume 365, Page(s) l1875

MeSH term(s)	Brain Injuries/diagnosis ; Child ; Head Injuries, Closed/diagnosis ; Humans ; Pediatrics/methods ; Practice Guidelines as Topic ; Tomography, X-Ray Computed ; Vomiting/diagnosis
Language	English
Publishing date	2019-05-23
Publishing country	England
Document type	Journal Article
ZDB-ID	1362901-3
ISSN	1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
ISSN (online)	1756-1833
ISSN	0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
DOI	10.1136/bmj.l1875
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Article ; Online: Ex-vivo drug screening of surgically resected glioma stem cells to replace murine avatars and provide personalise cancer therapy for glioblastoma patients.

Gagg, Hannah / Williams, Sophie T / Conroy, Samantha / Myers, Katie N / McGarrity-Cottrell, Connor / Jones, Callum / Helleday, Thomas / Rantala, Juha / Rominiyi, Ola / Danson, Sarah J / Collis, Spencer J / Wells, Greg

F1000Research

2024 Volume 12, Page(s) 954

Abstract: With diminishing returns and high clinical failure rates from traditional preclinical and animal-based drug discovery strategies, more emphasis is being placed on alternative drug discovery platforms. ...

Abstract	With diminishing returns and high clinical failure rates from traditional preclinical and animal-based drug discovery strategies, more emphasis is being placed on alternative drug discovery platforms.
MeSH term(s)	Humans ; Animals ; Mice ; Glioblastoma/drug therapy ; Drug Evaluation, Preclinical ; Avatar ; Brain Neoplasms/drug therapy ; Early Detection of Cancer ; Glioma ; Neoplastic Stem Cells
Language	English
Publishing date	2024-03-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2699932-8
ISSN	2046-1402 ; 2046-1402
ISSN (online)	2046-1402
ISSN	2046-1402
DOI	10.12688/f1000research.135809.2
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Article ; Online: Correction: Tumour treating fields therapy for glioblastoma: current advances and future directions.

Rominiyi, Ola / Vanderlinden, Aurelie / Clenton, Susan Jane / Bridgewater, Caroline / Al-Tamimi, Yahia / Collis, Spencer James

British journal of cancer

2021 Volume 125, Issue 4, Page(s) 623

Language	English
Publishing date	2021-06-10
Publishing country	England
Document type	Published Erratum
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-021-01451-5
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Article ; Online: Tumour treating fields therapy for glioblastoma: current advances and future directions.

Rominiyi, Ola / Vanderlinden, Aurelie / Clenton, Susan Jane / Bridgewater, Caroline / Al-Tamimi, Yahia / Collis, Spencer James

British journal of cancer

2020 Volume 124, Issue 4, Page(s) 697–709

Abstract: Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition of tumour-treating fields (TTFields)-an approach in ... ...

Abstract	Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition of tumour-treating fields (TTFields)-an approach in which alternating electrical fields exert biophysical force on charged and polarisable molecules known as dipoles-to standard therapy, has been shown to extend survival for patients with newly diagnosed GBM, recurrent GBM and mesothelioma, leading to the clinical approval of this approach by the FDA. TTFields represent a non-invasive anticancer modality consisting of low-intensity (1-3 V/cm), intermediate-frequency (100-300 kHz), alternating electric fields delivered via cutaneous transducer arrays configured to provide optimal tumour-site coverage. Although TTFields were initially demonstrated to inhibit cancer cell proliferation by interfering with mitotic apparatus, it is becoming increasingly clear that TTFields show a broad mechanism of action by disrupting a multitude of biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects. This review describes advances in our current understanding of the mechanisms by which TTFields mediate anticancer effects. Additionally, we summarise the landscape of TTFields clinical trials across various cancers and consider how emerging preclinical data might inform future clinical applications for TTFields.
MeSH term(s)	Animals ; Brain Neoplasms/pathology ; Brain Neoplasms/therapy ; Clinical Trials, Phase III as Topic ; Electric Stimulation Therapy/methods ; Glioblastoma/pathology ; Glioblastoma/therapy ; Humans ; Randomized Controlled Trials as Topic
Language	English
Publishing date	2020-11-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-020-01136-5
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Article ; Online: Precision oncology using ex vivo technology: a step towards individualised cancer care?

Williams, Sophie T / Wells, Greg / Conroy, Samantha / Gagg, Hannah / Allen, Richard / Rominiyi, Ola / Helleday, Thomas / Hullock, Katie / Pennington, Catherine E W / Rantala, Juha / Collis, Spencer J / Danson, Sarah J

Expert reviews in molecular medicine

2022 Volume 24, Page(s) e39

Abstract: Despite advances in cancer genomics and the increased use of genomic medicine, metastatic cancer is still mostly an incurable and fatal disease. With diminishing returns from traditional drug discovery strategies, and high clinical failure rates, more ... ...

Abstract	Despite advances in cancer genomics and the increased use of genomic medicine, metastatic cancer is still mostly an incurable and fatal disease. With diminishing returns from traditional drug discovery strategies, and high clinical failure rates, more emphasis is being placed on alternative drug discovery platforms, such as ex vivo approaches. Ex vivo approaches aim to embed biological relevance and inter-patient variability at an earlier stage of drug discovery, and to offer more precise treatment stratification for patients. However, these techniques also have a high potential to offer personalised therapies to patients, complementing and enhancing genomic medicine. Although an array of approaches are available to researchers, only a minority of techniques have made it through to direct patient treatment within robust clinical trials. Within this review, we discuss the current challenges to ex vivo approaches within clinical practice and summarise the contemporary literature which has directed patient treatment. Finally, we map out how ex vivo approaches could transition from a small-scale, predominantly research based technology to a robust and validated predictive tool. In future, these pre-clinical approaches may be integrated into clinical cancer pathways to assist in the personalisation of therapy choices and to hopefully improve patient experiences and outcomes.
MeSH term(s)	Humans ; Neoplasms/therapy ; Neoplasms/drug therapy ; Precision Medicine/methods ; Medical Oncology/methods ; Genomics/methods
Language	English
Publishing date	2022-10-03
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ISSN	1462-3994
ISSN (online)	1462-3994
DOI	10.1017/erm.2022.32
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