RARE DISEASE
Hereditary retinoblastoma
Hereditary retinoblastoma
Hereditary retinoblastoma
Drug discovery
2
drugs
With orphan designations
Overview
Hereditary retinoblastoma is caused by germline RB1 mutations, predisposing patients to bilateral retinal tumors typically diagnosed by age 2. It accounts for 40% of cases [2][6][14] and confers lifelong risks of trilateral retinoblastoma (pineal tumors) [1][11] and secondary malignancies (osteosarcoma, melanoma) [7][15]. Genetic counseling and RB1 testing are critical for family risk assessment [1][11][19].
Categories: rare genetic diseases, rare neoplastic diseases, rare ophthalmic disorders
Research Papers
314 drug discovery papers about Hereditary retinoblastoma, with 1 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
314 drug discovery papers about Hereditary retinoblastoma, with 1 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2025-08-13 | Retinoblastoma: Evolving Concepts and Future Challenges
Retinoblastoma is the most common ocular malignancy in children. It results from mutations in the RB1 gene or from MYCN oncogene amplification. We distinguish between the more common unilateral form and the rarer bilateral form. It is important to note that bilateral retinoblastoma is always hereditary. The most common and characteristic symptom is the white pupillary reflex. In addition, the child may develop strabismus or heterochromia. Treatment methods vary, ranging from those aimed at salvaging the eye to those involving total enucleation. Prognosis depends on the location and stage of the tumor. This review aims to explore the literature on new therapeutic methods and recent discoveries in the field of retinoblastoma.
2025-04-25 | Epigenetic Reprogramming by Decitabine in Retinoblastoma
Introduction: Retinoblastoma (Rb) is a rare cancer, yet it is the most common eye tumor in children. It can occur in either a familial or sporadic form, with the sporadic variant being more prevalent, though its downstream effects on epigenetic markers remain largely unclear. Currently, the treatment for retinoblastoma typically involves aggressive chemotherapy and surgical resection. The identification of specific epigenetic characteristics of non-hereditary (sporadic) Rb has led to the development of advanced, high-throughput methods to explore its epigenetic profile. Our previous research demonstrated that treatment with the demethylating agent 5-Aza-2′-deoxycytidine (decitabine; DAC) induced cell cycle arrest and apoptosis in a well-characterized retinoblastoma model (WERI-Rb-1). Our analysis of time-dependent gene expression in WERI-Rb-1 cells following DAC exposure has led to the development of testable hypotheses to further investigate the epigenetic impact on the initiation and progression of retinoblastoma tumors. Methods: Gene expression analysis of publicly available datasets from patients’ primary tumors and normal retina have been compared with those found in WERI-Rb-1 cells to assess the relevance of DAC-driven genes as markers of primary retinoblastoma tumors. The effect of DAC treatment has been evaluated in vivo, both in subcutaneous xenografts and in orthotopic models. qPCR analysis of gene expression and Methylation-Specific PCR (MSP) was performed. Results: Our analysis of network maps for differentially expressed genes in primary tumors compared to DAC-driven genes identified 15 hub/driver genes that may play a pivotal role in the genesis and progression of retinoblastoma. DAC treatment induced significant tumor growth arrest in vivo in both subcutaneous and orthotopic xenograft retinoblastoma models. This was associated with changes in gene expression, either through the direct switching-on of epigenetically locked genes or through the indirect regulation of linked genes, suggesting the potential use of DAC as an epigenetic anti-cancer drug for the treatment of retinoblastoma patients. Conclusion: There is a pressing need to develop innovative treatments for retinoblastoma. Our research revealed that DAC can effectively suppress the growth and progression of retinoblastoma in in vivo models, offering a potential new therapeutic approach to battle this destructive disease. This discovery highlights the impact of this epigenetic therapy in reprogramming tumor dynamics, and thus its potential to preserve both the vision and lives of affected children.
2024-12-30 | Expression of Wnt signaling proteins LEF1, β-catenin, GSK3β, DVL1, and N-myc varies across retinoblastoma subtypes and pRb phosphorylation status
Retinoblastoma, a rare childhood eye cancer, has hereditary and non-hereditary forms. While TNM classification helps in prognosis, understanding molecular mechanisms is vital for the clinical behavior of retinoblastoma prediction. Our study aimed to analyze the expression levels of key Wnt pathway proteins, GSK3β, LEF1, β-catenin, and DVL1, and associate them to non-phosphorylated active form (pRb) and the phosphorylated inactive form (ppRb) and N-myc expression, in retinoblastoma cells and healthy retinal cells, in order to elucidate their roles in retinoblastoma and identify potential targets that could help to improve diagnostic and therapy. Specimens from 22 retinoblastoma cases (unilateral, bilateral, and trilateral) were analyzed. Immunohistochemistry assessed proteins' expressions, followed by semi-quantitative analysis using the Immunoreactivity Score (IRS). Bayesian statistical methods were employed for data analysis. The study revealed various expression patterns of Wnt signaling proteins across different retinoblastoma types. The high expression levels were observed for LEF1 and DVL1. Inactive GSK3β and nuclear localization of β-catenin indicated Wnt signaling activation. The levels of inactive ppRb were significantly higher in retinoblastoma compared to healthy retina, as well as the levels of inactive GSK3β. Positive correlations between DVL1 and N-myc, GSK3β Y216 and GSK3β S9 and non-P β-catenin and LEF1 were established. Retinoblastomas without germline mutations (RB1+/+) exhibited high pRb, N-myc, and LEF1 levels, while those in genetically predisposed children (RB1+/-) showed lower expression of these proteins. Trilateral retinoblastomas demonstrated especially high N-myc and LEF1, but low pRb and ppRb levels. The findings highlight the meaningful role of the Wnt signaling pathway in retinoblastoma pathogenesis, providing insights into potential therapeutic targets. Understanding molecular features may pave the way for personalized treatments and improve outcomes for retinoblastoma patients.
2024-03-18 | Therapeutic Strategies for RB1-Deficient Cancers: Intersecting Gene Regulation and Targeted Therapy
The retinoblastoma (RB) transcriptional corepressor 1 (RB1) is a critical tumor suppressor gene, governing diverse cellular processes implicated in cancer biology. Dysregulation or deletion in RB1 contributes to the development and progression of various cancers, making it a prime target for therapeutic intervention. RB1's canonical function in cell cycle control and DNA repair mechanisms underscores its significance in restraining aberrant cell growth and maintaining genomic stability. Understanding the complex interplay between RB1 and cellular pathways is beneficial to fully elucidate its tumor-suppressive role across different cancer types and for therapeutic development. As a result, investigating vulnerabilities arising from RB1 deletion-associated mechanisms offers promising avenues for targeted therapy. Recently, several findings highlighted multiple methods as a promising strategy for combating tumor growth driven by RB1 loss, offering potential clinical benefits in various cancer types. This review summarizes the multifaceted role of RB1 in cancer biology and its implications for targeted therapy.
2024-03-15 | Advancement in the treatment, genetic understanding, and diagnostic approaches for retinoblastoma
The most common intraocular tumor in children is retinoblastoma. In developed countries, there has been an impressive rise in the survival rate and visual outcome of patients with retinoblastoma. This is clarified by developments in retinoblastoma treatment and early detection of tumors. The primary therapy remedy for intraocular retinoblastoma is now chemotherapy along with adjuvant consolidative treatment, instead of external beam radiation. Likewise, prophylactic chemotherapy is now allowed to treat potential micro metastases in enucleated eyes based on the identification of high-risk histopathological factors. Extra ocular retinoblastoma still has a poor future outcome; chances of survival have been reported to be between 50% and 70%. Retinoblastoma patients' overall survival is still struggling in developing countries, mostly because of delayed presentation and greater risk of extra ocular illness while compared to with the developed world, where intraocular disease contributes to majority of cases. To enhance the survival rate for those with retinoblastoma in developing countries, greater priority must be given to early detection of tumors. We provide a summary of the latest clinical management of retinoblastoma in this article.
2025-08-13 | Retinoblastoma: Evolving Concepts and Future Challenges
Retinoblastoma is the most common ocular malignancy in children. It results from mutations in the RB1 gene or from MYCN oncogene amplification. We distinguish between the more common unilateral form and the rarer bilateral form. It is important to note that bilateral retinoblastoma is always hereditary. The most common and characteristic symptom is the white pupillary reflex. In addition, the child may develop strabismus or heterochromia. Treatment methods vary, ranging from those aimed at salvaging the eye to those involving total enucleation. Prognosis depends on the location and stage of the tumor. This review aims to explore the literature on new therapeutic methods and recent discoveries in the field of retinoblastoma.
2025-04-25 | Epigenetic Reprogramming by Decitabine in Retinoblastoma
Introduction: Retinoblastoma (Rb) is a rare cancer, yet it is the most common eye tumor in children. It can occur in either a familial or sporadic form, with the sporadic variant being more prevalent, though its downstream effects on epigenetic markers remain largely unclear. Currently, the treatment for retinoblastoma typically involves aggressive chemotherapy and surgical resection. The identification of specific epigenetic characteristics of non-hereditary (sporadic) Rb has led to the development of advanced, high-throughput methods to explore its epigenetic profile. Our previous research demonstrated that treatment with the demethylating agent 5-Aza-2′-deoxycytidine (decitabine; DAC) induced cell cycle arrest and apoptosis in a well-characterized retinoblastoma model (WERI-Rb-1). Our analysis of time-dependent gene expression in WERI-Rb-1 cells following DAC exposure has led to the development of testable hypotheses to further investigate the epigenetic impact on the initiation and progression of retinoblastoma tumors. Methods: Gene expression analysis of publicly available datasets from patients’ primary tumors and normal retina have been compared with those found in WERI-Rb-1 cells to assess the relevance of DAC-driven genes as markers of primary retinoblastoma tumors. The effect of DAC treatment has been evaluated in vivo, both in subcutaneous xenografts and in orthotopic models. qPCR analysis of gene expression and Methylation-Specific PCR (MSP) was performed. Results: Our analysis of network maps for differentially expressed genes in primary tumors compared to DAC-driven genes identified 15 hub/driver genes that may play a pivotal role in the genesis and progression of retinoblastoma. DAC treatment induced significant tumor growth arrest in vivo in both subcutaneous and orthotopic xenograft retinoblastoma models. This was associated with changes in gene expression, either through the direct switching-on of epigenetically locked genes or through the indirect regulation of linked genes, suggesting the potential use of DAC as an epigenetic anti-cancer drug for the treatment of retinoblastoma patients. Conclusion: There is a pressing need to develop innovative treatments for retinoblastoma. Our research revealed that DAC can effectively suppress the growth and progression of retinoblastoma in in vivo models, offering a potential new therapeutic approach to battle this destructive disease. This discovery highlights the impact of this epigenetic therapy in reprogramming tumor dynamics, and thus its potential to preserve both the vision and lives of affected children.
2024-12-30 | Expression of Wnt signaling proteins LEF1, β-catenin, GSK3β, DVL1, and N-myc varies across retinoblastoma subtypes and pRb phosphorylation status
Retinoblastoma, a rare childhood eye cancer, has hereditary and non-hereditary forms. While TNM classification helps in prognosis, understanding molecular mechanisms is vital for the clinical behavior of retinoblastoma prediction. Our study aimed to analyze the expression levels of key Wnt pathway proteins, GSK3β, LEF1, β-catenin, and DVL1, and associate them to non-phosphorylated active form (pRb) and the phosphorylated inactive form (ppRb) and N-myc expression, in retinoblastoma cells and healthy retinal cells, in order to elucidate their roles in retinoblastoma and identify potential targets that could help to improve diagnostic and therapy. Specimens from 22 retinoblastoma cases (unilateral, bilateral, and trilateral) were analyzed. Immunohistochemistry assessed proteins' expressions, followed by semi-quantitative analysis using the Immunoreactivity Score (IRS). Bayesian statistical methods were employed for data analysis. The study revealed various expression patterns of Wnt signaling proteins across different retinoblastoma types. The high expression levels were observed for LEF1 and DVL1. Inactive GSK3β and nuclear localization of β-catenin indicated Wnt signaling activation. The levels of inactive ppRb were significantly higher in retinoblastoma compared to healthy retina, as well as the levels of inactive GSK3β. Positive correlations between DVL1 and N-myc, GSK3β Y216 and GSK3β S9 and non-P β-catenin and LEF1 were established. Retinoblastomas without germline mutations (RB1+/+) exhibited high pRb, N-myc, and LEF1 levels, while those in genetically predisposed children (RB1+/-) showed lower expression of these proteins. Trilateral retinoblastomas demonstrated especially high N-myc and LEF1, but low pRb and ppRb levels. The findings highlight the meaningful role of the Wnt signaling pathway in retinoblastoma pathogenesis, providing insights into potential therapeutic targets. Understanding molecular features may pave the way for personalized treatments and improve outcomes for retinoblastoma patients.
2024-03-18 | Therapeutic Strategies for RB1-Deficient Cancers: Intersecting Gene Regulation and Targeted Therapy
The retinoblastoma (RB) transcriptional corepressor 1 (RB1) is a critical tumor suppressor gene, governing diverse cellular processes implicated in cancer biology. Dysregulation or deletion in RB1 contributes to the development and progression of various cancers, making it a prime target for therapeutic intervention. RB1's canonical function in cell cycle control and DNA repair mechanisms underscores its significance in restraining aberrant cell growth and maintaining genomic stability. Understanding the complex interplay between RB1 and cellular pathways is beneficial to fully elucidate its tumor-suppressive role across different cancer types and for therapeutic development. As a result, investigating vulnerabilities arising from RB1 deletion-associated mechanisms offers promising avenues for targeted therapy. Recently, several findings highlighted multiple methods as a promising strategy for combating tumor growth driven by RB1 loss, offering potential clinical benefits in various cancer types. This review summarizes the multifaceted role of RB1 in cancer biology and its implications for targeted therapy.
2024-03-15 | Advancement in the treatment, genetic understanding, and diagnostic approaches for retinoblastoma
The most common intraocular tumor in children is retinoblastoma. In developed countries, there has been an impressive rise in the survival rate and visual outcome of patients with retinoblastoma. This is clarified by developments in retinoblastoma treatment and early detection of tumors. The primary therapy remedy for intraocular retinoblastoma is now chemotherapy along with adjuvant consolidative treatment, instead of external beam radiation. Likewise, prophylactic chemotherapy is now allowed to treat potential micro metastases in enucleated eyes based on the identification of high-risk histopathological factors. Extra ocular retinoblastoma still has a poor future outcome; chances of survival have been reported to be between 50% and 70%. Retinoblastoma patients' overall survival is still struggling in developing countries, mostly because of delayed presentation and greater risk of extra ocular illness while compared to with the developed world, where intraocular disease contributes to majority of cases. To enhance the survival rate for those with retinoblastoma in developing countries, greater priority must be given to early detection of tumors. We provide a summary of the latest clinical management of retinoblastoma in this article.
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Drug Discovery Landscape
2 orphan drug designations for Hereditary retinoblastoma.
2 orphan drug designations for Hereditary retinoblastoma.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
melphalan | small molecules | FDA | 2025-07-24 | — | Zhaoke Ophthalmology |
Genetically modified human adenovirus encoding human PH20 hyaluronidase | gene therapies | EMA | 2024-10-11 | — | Theriva Biologics S.L. |
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