The predictive capacity of in vitro preclinical models to evaluate drugs for the treatment of retinoblastoma

Sinenko, Irina; Turnell-Ritson, Roland C.; Munier, Francis L.; Dyson, Paul

doi:10.1016/j.exer.2023.109447

Cited by 2 publications

(5 citation statements)

References 113 publications

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“…Notably, Y79-derived tumors in xenograft models mimic invasive and metastatic disease, contrasting with the non-metastatic ocular tumors produced by WERI-Rb1 [28]. Moreover, other cell lines derived from unilateral and bilateral retinoblastomas have provided valuable insights into the neuronal phenotypes associated with different RB1 gene mutations and/or additional non-RB1 mutations [29,30]. Resistance to drugs and the recurrence of cancer after treatment are primary concerns associated with chemotherapy, which remains the primary method for preserving the eye in retinoblastoma treatment.…”

Section: Retinoblastoma Pre-clinical Modelsmentioning

confidence: 99%

“…In recent years, there has been a significant transition towards utilizing three-dimensional (3D) cell culture models in retinoblastoma research due to limitations of traditional 2D cultures in capturing disease complexity and drug responses accurately. An ideal 3D culture system for retinoblastoma should faithfully replicate the pathophysiological features of the disease, encompassing genomic traits, gene/protein expression profiles, and responses to therapeutic agents [30]. It should also accommodate various treatment approaches and be scalable for large drug screenings [31].…”

Section: Retinoblastoma Pre-clinical Modelsmentioning

confidence: 99%

“…Retinal organoids generated from stem cells represent another exciting avenue for retinoblastoma disease modeling and drug screening. These organoids can be differentiated into multiple cell types found in the retina and can replicate disease processes such as retinoblastoma tumorigenesis [30]. Nonetheless, challenges like extended maturation periods and maintenance requirements presently constrain their extensive adoption for routine drug screening.…”

Section: Retinoblastoma Pre-clinical Modelsmentioning

confidence: 99%

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Histone Deacetylases in Retinoblastoma

Lisek,

Tomczak,

Swiatek

et al. 2024

IJMS

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Retinoblastoma, a pediatric ocular malignancy, presents significant challenges in comprehending its molecular underpinnings and targeted therapeutic approaches. The dysregulated activity of histone deacetylases (HDACs) has been associated with retinoblastoma pathogenesis, influencing critical cellular processes like cell cycle regulation or retinal ganglion cell apoptosis. Through their deacetylase activity, HDACs exert control over key tumor suppressors and oncogenes, influencing the delicate equilibrium between proliferation and cell death. Furthermore, the interplay between HDACs and the retinoblastoma protein pathway, a pivotal aspect of retinoblastoma etiology, reveals a complex network of interactions influencing the tumor microenvironment. The examination of HDAC inhibitors, encompassing both established and novel compounds, offers insights into potential approaches to restore acetylation balance and impede retinoblastoma progression. Moreover, the identification of specific HDAC isoforms exhibiting varying expression in retinoblastoma provides avenues for personalized therapeutic strategies, allowing for interventions tailored to individual patient profiles. This review focuses on the intricate interrelationship between HDACs and retinoblastoma, shedding light on epigenetic mechanisms that control tumor development and progression. The exploration of HDAC-targeted therapies underscores the potential for innovative treatment modalities in the pursuit of more efficacious and personalized management strategies for this disease.

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Section: Retinoblastoma Pre-clinical Modelsmentioning

confidence: 99%

Section: Retinoblastoma Pre-clinical Modelsmentioning

confidence: 99%

Section: Retinoblastoma Pre-clinical Modelsmentioning

confidence: 99%

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Histone Deacetylases in Retinoblastoma

Lisek,

Tomczak,

Swiatek

et al. 2024

IJMS

View full text Add to dashboard Cite

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“…Preclinical retinoblastoma models include cellular models and animal models (both transgenic and xenograft) 16–19 . While in vivo transgenic animal models, that is, GEMMs, are able to depict some tumorigenic aspects of the disease, there are genomic and epigenomic differences between mice and humans 21 .…”

Section: Introductionmentioning

confidence: 99%

“…Preclinical retinoblastoma models include cellular models and animal models (both transgenic and xenograft). 16 , 17 , 18 , 19 , 20 While in vivo transgenic animal models, that is, GEMMs, are able to depict some tumorigenic aspects of the disease, there are genomic and epigenomic differences between mice and humans. 21 Particularly in the case of retinoblastoma, as the cell of origin is different in these two species, mice are not an optimal organism to study this specific disease.…”

Section: Introductionmentioning

confidence: 99%

Translational screening platform to evaluate chemotherapy in combination with focal therapy for retinoblastoma

et al. 2023

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Retinoblastoma is the most common pediatric eye cancer. It is currently treated with a limited number of drugs, adapted from other pediatric cancer treatments. Drug toxicity and relapse of the disease warrant new therapeutic strategies for these young patients. In this study, we developed a robust tumoroid‐based platform to test chemotherapeutic agents in combination with focal therapy (thermotherapy) – a treatment option widely used in clinical practice – in accordance with clinically relevant trial protocols. The model consists of matrix‐embedded tumoroids that retain retinoblastoma features and respond to repeated chemotherapeutic drug exposure similarly to advanced clinical cases. Moreover, the screening platform includes a diode laser (810 nm, 0.3 W) to selectively heat the tumoroids, combined with an on‐line system to monitor the intratumoral and surrounding temperatures. This allows the reproduction of the clinical settings of thermotherapy and combined chemothermotherapy treatments. When testing the two main drugs currently used in clinics to treat retinoblastoma in our model, we observed results similar to those clinically obtained, validating the utility of the model. This screening platform is the first system to accurately reproduce clinically relevant treatment methods and should lead to the identification of more efficient drugs to treat retinoblastoma.

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The predictive capacity of in vitro preclinical models to evaluate drugs for the treatment of retinoblastoma

Cited by 2 publications

References 113 publications

Histone Deacetylases in Retinoblastoma

Histone Deacetylases in Retinoblastoma

Translational screening platform to evaluate chemotherapy in combination with focal therapy for retinoblastoma

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