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1.
Cancer Sci ; 114(9): 3728-3739, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37340597

ABSTRACT

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.


Subject(s)
Retinal Neoplasms , Retinoblastoma , Child , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Neoplasm Recurrence, Local/drug therapy , Retinal Neoplasms/drug therapy , Retinoblastoma/drug therapy
2.
Exp Eye Res ; 230: 109447, 2023 05.
Article in English | MEDLINE | ID: mdl-36940901

ABSTRACT

Retinoblastoma is a rare childhood cancer of the eye. Of the small number of drugs are used to treat retinoblastoma, all have been repurposed from drugs developed for other conditions. In order to find drugs or drug combinations better suited to the improved treatment of retinoblastoma, reliable predictive models are required, which facilitate the challenging transition from in vitro studies to clinical trials. In this review, the research performed to date on the development of 2D and 3D in vitro models for retinoblastoma is presented. Most of this research was undertaken with a view to better biological understanding of retinoblastoma, and we discuss the potential for these models to be applied to drug screening. Future research directions for streamlined drug discovery are considered and evaluated, and many promising avenues identified.


Subject(s)
Retinal Neoplasms , Retinoblastoma , Humans , Child , Retinoblastoma/drug therapy , Drug Evaluation, Preclinical , Retinal Neoplasms/drug therapy
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