Improved cell-specificity of adeno-associated viral vectors for medullary thyroid carcinoma using calcitonin gene regulatory elements

Levy, Hazel C.; Hulvey, Danielle; Adamson-Small, Laura; Jn-Simon, Natacha; Prima, Victor; Rivkees, Scott A.; Hobbs, Jacqueline A.

doi:10.1371/journal.pone.0228005

Cited by 3 publications

(1 citation statement)

References 49 publications

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“…However, ensuring a safe, targeted delivery mechanism to cancer cells while sparing healthy tissues remains a challenge and warrants further research ( Rizwanullah et al, 2021 ). Approaches such as viral vectors are being explored to improve cell type specificity ( Levy et al, 2020 ). In addition, the ethical issues associated with gene editing cannot be understated.…”

Section: Gene Editing Technologies and Their Potential In Pediatric C...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: Gene Editing Technologies and Their Potential In Pediatric C...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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Assessment of AXL and mTOR genes expression in medullary thyroid carcinoma (MTC) cell line in relation with over expression of miR-144 and miR-34a

Pishkari

Hadavi

Koochaki

et al. 2021

Hormone Molecular Biology and Clinical Investigation

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Objectives The aim of the present study was to investigate the expression of AXL and mTOR genes and their targeting microRNAs (miRNAs) including miR-34a and miR-144 in Medullary Thyroid Carcinoma (MTC) cell line, TT, and determine the effect of these two miRNAs on their target genes to introduce new molecular markers or therapeutics. Methods The expression of miR-34a, miR-144, and their targets genes including AXL and mTOR was evaluated by quantitative Real-time PCR. Luciferase assay was performed to confirm the interaction between miRNAs and their target mRNAs. The expression level of AXL and mTOR was evaluated before and after miRNAs induction in TT cell line compared with Cos7 as control cells. Results The expression of AXL and mTOR were up-regulated significantly, while miR-34a and miR-144 were down-regulated in TT cell line compared to Cos7. After transduction, the overexpression of miR-34a and 144 caused down-regulation of both genes. Luciferase assay results showed that the mTOR is targeted by miR-34a and miR-144 and the intensity of luciferase decreased in the presence of miRNAs. Conclusions Based on the results of the present study and since AXL and mTOR genes play a critical role in variety of human cancers, suppression of these genes by their targeting miRNAs, especially miR-34a and miR-144, can be propose as a new strategy for MTC management. However, more studies are needed to approve the hypothesis.

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Looking at Thyroid Cancer from the Tumor-Suppressor Genes Point of View

Rajabi

Alix‐Panabières

Alaei

et al. 2022

Cancers

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Thyroid cancer is the most frequent endocrine malignancy and accounts for approximately 1% of all diagnosed cancers. A variety of mechanisms are involved in the transformation of a normal tissue into a malignant one. Loss of tumor-suppressor gene (TSG) function is one of these mechanisms. The normal functions of TSGs include cell proliferation and differentiation control, genomic integrity maintenance, DNA damage repair, and signaling pathway regulation. TSGs are generally classified into three subclasses: (i) gatekeepers that encode proteins involved in cell cycle and apoptosis control; (ii) caretakers that produce proteins implicated in the genomic stability maintenance; and (iii) landscapers that, when mutated, create a suitable environment for malignant cell growth. Several possible mechanisms have been implicated in TSG inactivation. Reviewing the various TSG alteration types detected in thyroid cancers may help researchers to better understand the TSG defects implicated in the development/progression of this cancer type and to find potential targets for prognostic, predictive, diagnostic, and therapeutic purposes. Hence, the main purposes of this review article are to describe the various TSG inactivation mechanisms and alterations in human thyroid cancer, and the current therapeutic options for targeting TSGs in thyroid cancer.

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Improved cell-specificity of adeno-associated viral vectors for medullary thyroid carcinoma using calcitonin gene regulatory elements

Cited by 3 publications

References 49 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

Assessment of AXL and mTOR genes expression in medullary thyroid carcinoma (MTC) cell line in relation with over expression of miR-144 and miR-34a

Looking at Thyroid Cancer from the Tumor-Suppressor Genes Point of View

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