Role of epigenetic mechanisms in propagating off-targeted effects following radiation based therapies – A review

Swati, Swati; Chadha, Vijayta Dani

doi:10.1016/j.mrrev.2021.108370

Cited by 3 publications

(1 citation statement)

References 138 publications

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“…Another mechanism of resistance is through mutations in targets that allow evasion of antibodies ( da Silva, 2012 ). Notably, even targeted therapies may have adverse effects due to non-specific distribution ( Swati, 2021 ).…”

Section: Advantages and Limitations Of Gene Therapy In The Context Of...mentioning

confidence: 99%

Advances and challenges in gene therapy strategies for pediatric cancer: a comprehensive update

Moaveni,

Amiri,

Shademan

et al. 2024

Front. Mol. Biosci.

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Pediatric cancers represent a tragic but also promising area for gene therapy. Although conventional treatments have improved survival rates, there is still a need for targeted and less toxic interventions. This article critically analyzes recent advances in gene therapy for pediatric malignancies and discusses the challenges that remain. We explore the innovative vectors and delivery systems that have emerged, such as adeno-associated viruses and non-viral platforms, which show promise in addressing the unique pathophysiology of pediatric tumors. Specifically, we examine the field of chimeric antigen receptor (CAR) T-cell therapies and their adaptation for solid tumors, which historically have been more challenging to treat than hematologic malignancies. We also discuss the genetic and epigenetic complexities inherent to pediatric cancers, such as tumor heterogeneity and the dynamic tumor microenvironment, which pose significant hurdles for gene therapy. Ethical considerations specific to pediatric populations, including consent and long-term follow-up, are also analyzed. Additionally, we scrutinize the translation of research from preclinical models that often fail to mimic pediatric cancer biology to the regulatory landscapes that can either support or hinder innovation. In summary, this article provides an up-to-date overview of gene therapy in pediatric oncology, highlighting both the rapid scientific progress and the substantial obstacles that need to be addressed. Through this lens, we propose a roadmap for future research that prioritizes the safety, efficacy, and complex ethical considerations involved in treating pediatric patients. Our ultimate goal is to move from incremental advancements to transformative therapies.

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Section: Advantages and Limitations Of Gene Therapy In The Context Of...mentioning

confidence: 99%

Advances and challenges in gene therapy strategies for pediatric cancer: a comprehensive update

Moaveni,

Amiri,

Shademan

et al. 2024

Front. Mol. Biosci.

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Ionizing Radiation as a Carcinogen

Jones,

Karouia,

Cristea

et al. 2024

Reference Module in Biomedical Sciences

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Targeted and Non-Targeted Mechanisms for Killing Hypoxic Tumour Cells—Are There New Avenues for Treatment?

Apilan

Mothersill

2021

IJMS

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Purpose: A major issue in radiotherapy is the relative resistance of hypoxic cells to radiation. Historic approaches to this problem include the use of oxygen mimetic compounds to sensitize tumour cells, which were unsuccessful. This review looks at modern approaches aimed at increasing the efficacy of targeting and radiosensitizing hypoxic tumour microenvironments relative to normal tissues and asks the question of whether non-targeted effects in radiobiology may provide a new “target”. Novel techniques involve the integration of recent technological advancements such as nanotechnology, cell manipulation, and medical imaging. Particularly, the major areas of research discussed in this review include tumour hypoxia imaging through PET imaging to guide carbogen breathing, gold nanoparticles, macrophage-mediated drug delivery systems used for hypoxia-activate prodrugs, and autophagy inhibitors. Furthermore, this review outlines several features of these methods, including the mechanisms of action to induce radiosensitization, the increased accuracy in targeting hypoxic tumour microenvironments relative to normal tissue, preclinical/clinical trials, and future considerations. Conclusions: This review suggests that the four novel tumour hypoxia therapeutics demonstrate compelling evidence that these techniques can serve as powerful tools to increase targeting efficacy and radiosensitizing hypoxic tumour microenvironments relative to normal tissue. Each technique uses a different way to manipulate the therapeutic ratio, which we have labelled “oxygenate, target, use, and digest”. In addition, by focusing on emerging non-targeted and out-of-field effects, new umbrella targets are identified, which instead of sensitizing hypoxic cells, seek to reduce the radiosensitivity of normal tissues.

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Role of epigenetic mechanisms in propagating off-targeted effects following radiation based therapies – A review

Cited by 3 publications

References 138 publications

Advances and challenges in gene therapy strategies for pediatric cancer: a comprehensive update

Advances and challenges in gene therapy strategies for pediatric cancer: a comprehensive update

Ionizing Radiation as a Carcinogen

Targeted and Non-Targeted Mechanisms for Killing Hypoxic Tumour Cells—Are There New Avenues for Treatment?

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