-
Asia-Pacific Journal of Ophthalmology... Jul 2021
Topics: Humans; Retinal Neoplasms; Retinoblastoma; Skin Neoplasms
PubMed: 34284457
DOI: 10.1097/APO.0000000000000408 -
The FEBS Journal Aug 2022The retinoblastoma gene (RB1) was the first tumour suppressor cloned; the role of its protein product (RB) as the principal driver of the G1 checkpoint in cell cycle... (Review)
Review
The retinoblastoma gene (RB1) was the first tumour suppressor cloned; the role of its protein product (RB) as the principal driver of the G1 checkpoint in cell cycle control has been extensively studied. However, many other RB functions are continuously reported. Its role in senescence, DNA repair and apoptosis, among others, is indications of the significance of RB in a vast network of cellular interactions, explaining why RB loss or its malfunction is one of the leading causes of a large number of paediatric and adult cancers. RB was first reported in retinoblastoma, a common intraocular malignancy in the paediatric population worldwide. Currently, its diagnosis is clinical, and in nondeveloped countries, where the incidence is higher, it is performed in advanced stages of the disease, compromising the integrity of the eye and the patient's life. Even though new treatments are being continuously developed, enucleation is still a major choice due to the late disease stage diagnosis and treatments costs. Research into biomarkers is our best option to improve the chances of good results in the treatment and hopes of patients' good quality of life. Here, we recapitulated the history of the disease and the first treatments to put the advances in its clinical management into perspective. We also review the different functions of the protein and the progress in the search for biomarkers. It is clear that there is still a long way to go, but we should offer these children and their families a better way to deal with the disease with the community's effort.
Topics: Adult; Child; Genes, Tumor Suppressor; Humans; Quality of Life; Retinal Neoplasms; Retinoblastoma; Retinoblastoma Protein
PubMed: 34042282
DOI: 10.1111/febs.16035 -
JCO Oncology Practice Jun 2022Retinoblastoma is an aggressive pediatric eye cancer. Patient-reported outcome measures reveal important insights into how patients perceive their own health. Currently,...
PURPOSE
Retinoblastoma is an aggressive pediatric eye cancer. Patient-reported outcome measures reveal important insights into how patients perceive their own health. Currently, there is no widely used or validated measure for assessment of retinoblastoma outcomes. The purpose of this research was to uncover which treatment outcomes that retinoblastoma survivors and their parents value, to inform the development of a future measure.
METHODS
This qualitative, cross-sectional study included retinoblastoma survivors age 6 years and older and parents of retinoblastoma survivors. Participants who did not demonstrate fluency in English were excluded. Study participants participated in semistructured interviews or focus groups, either in person at The Hospital for Sick Children, Toronto, Canada, or through secure videoconference, between March 3, 2019, and January 25, 2020. Iterative rounds of opening coding, codebook development, and coresearcher analysis were used to identify key emergent themes and subthemes.
RESULTS
Seventeen adults participated in six focus groups. Nine pediatric survivors participated in individual interviews. Four common themes emerged from all participant groups: (1) definition of treatment success, (2) enucleation-acceptance and challenges, (3) treatment outcomes to measure, and (4) need for outcome reporting. An additional, unique theme was identified in all pediatric discussions: worries and coping mechanisms. Treatment outcomes deemed valuable were related to the following domains: psychosocial outcomes, daily functioning, functional vision, retinoblastoma education, cosmetic outcomes, and secondary eye conditions.
CONCLUSION
This study represents the first stage in the development of a retinoblastoma-specific patient-reported outcome measure. The findings reveal insight into what outcomes are valued by survivors after treatment and offer promise to improve outcomes assessment for retinoblastoma.
Topics: Adult; Child; Cross-Sectional Studies; Humans; Parents; Retinal Neoplasms; Retinoblastoma; Survivors
PubMed: 34985991
DOI: 10.1200/OP.21.00474 -
Seminars in Ophthalmology 2022Retinoblastoma (RB) is the most common intraocular malignancy in children. The diagnosis of RB is mainly based on clinical features and imaging characteristics.... (Review)
Review
PURPOSE
Retinoblastoma (RB) is the most common intraocular malignancy in children. The diagnosis of RB is mainly based on clinical features and imaging characteristics. Prognosis is based on stage of disease and response to treatment. In salvaged globes, direct tumor biopsy for genetic analysis and prognostication is an absolute contraindication at this point of time for the fear of extraocular tumor spread. Currently, there is a search for surrogate markers to allow accurate diagnosis and for prognostication, to predict the chances of globe salvage in RB. Therefore, biofluids such as plasma or aqueous humor have been studied to detect circulating tumor DNA (ctDNA) or cell-free DNA (cfDNA), respectively, to allow for treatment decision making, monitoring treatment response, and prognostic counselling.
METHODS
A search of electronic databases (PubMed, Google Scholar and MEDLINE) of all articles on liquid biopsy in retinoblastoma published in English was performed. The keywords used for the search included "retinoblastoma", "liquid biopsy", "aqueous humor" "circulating tumor cells", "cell-free DNA", "cfDNA", "circulating tumor DNA", "ctDNA", "tumor fraction", " mutation" and "SNCA". Additionally, historic articles on the advent of liquid biopsy in medicine were also reviewed. Pertinent cross-references from the studies were reviewed. Retrospective interventional and observational case series, observational case series, prospective cohort studies, reviews, case reports, surgical techniques, invited commentary and letters were included.
RESULTS
A total of 40 relevant articles were selected. Biomarkers in aqueous humor, serum and cerebrospinal fluid and their clinical applications are discussed.
CONCLUSION
Harvesting aqueous humor from eyes with retinoblastoma has been found safe and superior to blood for the detection of chromosomal changes. cfDNA from aqueous can be a surrogate marker to detect somatic copy number alterations and other genetic alterations in RB. ctDNA in plasma also has potential to help in diagnosis and prognosis of RB. Liquid biopsy in RB is an emerging topic, which could pave way for a better understanding of mechanisms for treatment response, resistance and recurrence in RB as well as possibly provide specific therapeutic targets to improve globe salvage.
Topics: Child; Humans; Retrospective Studies; Prospective Studies; Biomarkers, Tumor; Retinoblastoma; Circulating Tumor DNA; Mutation; Biopsy; Retinal Neoplasms
PubMed: 35604935
DOI: 10.1080/08820538.2022.2078165 -
Biosensors Mar 2021Retinoblastoma is a rare type of cancer, and its treatment, as well as diagnosis, is challenging, owing to mutations in the tumor-suppressor genes and lack of targeted,... (Review)
Review
Retinoblastoma is a rare type of cancer, and its treatment, as well as diagnosis, is challenging, owing to mutations in the tumor-suppressor genes and lack of targeted, efficient, cost-effective therapy, exhibiting a significant need for novel approaches to address these concerns. For this purpose, nanotechnology has revolutionized the field of medicine with versatile potential capabilities for both the diagnosis, as well as the treatment, of retinoblastoma via the targeted and controlled delivery of anticancer drugs via binding to the overexpressed retinoblastoma gene. Nanotechnology has also generated massive advancements in the treatment of retinoblastoma based on the use of surface-tailored multi-functionalized nanocarriers; overexpressed receptor-based nanocarriers ligands (folate, galactose, and hyaluronic acid); lipid-based nanocarriers; and metallic nanocarriers. These nanocarriers seem to benchmark in mitigating a plethora of malignant retinoblastoma via targeted delivery at a specified site, resulting in programmed apoptosis in cancer cells. The effectiveness of these nanoplatforms in diagnosing and treating intraocular cancers such as retinoblastoma has not been properly discussed, despite the increasing significance of nanomedicine in cancer management. This article reviewed the recent milestones and future development areas in the field of intraocular drug delivery and diagnostic platforms focused on nanotechnology.
Topics: Antineoplastic Agents; Drug Delivery Systems; Humans; Nanomedicine; Nanoparticles; Nanostructures; Nanotechnology; Neoplasms; Retinal Neoplasms; Retinoblastoma
PubMed: 33810621
DOI: 10.3390/bios11040097 -
BMC Medical Genomics Jul 2021India accounts for 20% of the global retinoblastoma (RB) burden. However, the existing data on RB1 gene germline mutations and its influence on clinical decisions is...
BACKGROUND
India accounts for 20% of the global retinoblastoma (RB) burden. However, the existing data on RB1 gene germline mutations and its influence on clinical decisions is minimally explored.
METHODS
Fifty children with RB underwent complete clinical examination and appropriate multidisciplinary management. Screening of germline RB1 gene mutations was performed through next-generation sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The mutation and non-mutation groups were compared for clinical parameters especially severity, progression and recurrence.
RESULTS
Twenty-nine patients had bilateral RB (BLRB) and 21 had unilateral RB (ULRB). The genetic analysis revealed 20 RB1 variations in 29 probands, inclusive of 3 novel mutations, known 16 mutations and heterozygous whole gene deletions. The mutation detection rate (MDR) was 86.2% in BLRB and 19% in ULRB. Associations of disease recurrence (p = 0.021), progression (p = 0.000) and higher percentage of optic nerve invasion, subretinal seeds and high-risk pathological factors were observed in the mutation group. Clinical management was influenced by the presence of germline mutations, particularly while deciding on enucleation, frequency of periodic follow up and radiotherapy.
CONCLUSIONS
We identified novel RB1 mutations, and our mutation detection rate was on par with the previous global studies. In our study, genetic results influenced clinical management and we suggest that it should be an essential and integral component of RB-care in India and elsewhere.
Topics: Retinoblastoma
PubMed: 34294096
DOI: 10.1186/s12920-021-01034-6 -
Journal of Pediatric Ophthalmology and... 2021To review the authors' experience in the diagnosis of retinoblastoma and to explore the frequency of intraocular conditions that mimic this malignancy according to... (Observational Study)
Observational Study
PURPOSE
To review the authors' experience in the diagnosis of retinoblastoma and to explore the frequency of intraocular conditions that mimic this malignancy according to patient age at presentation.
METHODS
This was a retrospective observational study including 549 patients (769 eyes) who were referred for confirmation and/or management of retinoblastoma between October 1998 and June 2019 at a single tertiary center. A detailed ocular examination was done by the same ocular oncologist under general anesthesia for every patient.
RESULTS
Of 549 patients referred for diagnostic confirmation or management of retinoblastoma, 393 (71.6%) patients were found to have retinoblastoma and 156 (28.4%) patients received the diagnosis of pseudoretinoblastoma. The mean patient age at presentation was 52.1 months, ranging from 1 to 276 months. The most common diagnoses among patients with pseudoretinoblastoma younger than 1 year were persistent fetal vasculature (PFV) (n = 19; 28.8%), Coats disease (n = 7; 10.6%), chorioretinal coloboma (n = 4; 6.1%), retinal dysplasia (n = 4; 6.1%), and retinal detachment (n = 4; 6.1%). In patients with pseudoretinoblastoma who were 1 to 5 years old, the most common diagnoses were Coats disease (n = 10; 25.6%), PFV (n = 7; 17.9%), and optic disc hypoplasia (n = 3; 7.7%). Patients older than 5 years were most likely to have Coats disease (n = 8; 15.7%), optic disc drusen (n = 5; 9.8%), retinopathy of prematurity (n = 4; 7.8%), and combined hamartoma (n = 4; 7.8%).
CONCLUSIONS
This study shows that 28.4% of patients referred for suspicion or management of retinoblastoma were classified as having pseudoretinoblastoma. The most common conditions causing diagnostic confusion with retinoblastoma included PFV and Coats disease, similar to previous publications from both high-and low-income countries. .
Topics: Child, Preschool; Diagnosis, Differential; Humans; Infant; Infant, Newborn; Persistent Hyperplastic Primary Vitreous; Retinal Neoplasms; Retinal Telangiectasis; Retinoblastoma; Retrospective Studies
PubMed: 34039153
DOI: 10.3928/01913913-20210108-01 -
Journal of Visualized Experiments : JoVE Oct 2022Human RB is pediatric cancer, which is lethal if no treatment is administered. As RB originates from cone precursors, which is relatively rare in rodent models,...
Human RB is pediatric cancer, which is lethal if no treatment is administered. As RB originates from cone precursors, which is relatively rare in rodent models, meanwhile regarding the interspecies differences between humans and rodents, a disease model derived from humans is more beneficial for uncovering the mechanisms of human RB and seeking the targets of therapy. Herein, the protocol describes the generation of two gene-edited hESC lines with a biallelic RB1 point mutation (RB1) and an RB1 knockout mutation (RB1), respectively. During the process of retinal development, the formation of RB is observed. The RB cell lines are also established by segregating from the RB organoids. Altogether, by differentiating the gene-edited hESC lines into the retinal organoids using a 2D and 3D combined differentiation protocol, we have successfully reconstructed the human RB in a dish and identified its cone-precursor origin. It would provide a helpful disease model for observing the retinoblastoma genesis, proliferation, and growth as well as further developing novel therapeutic agents.
Topics: Child; Humans; Retinoblastoma; Retinoblastoma Protein; Retinal Cone Photoreceptor Cells; Retina; Retinal Neoplasms
PubMed: 36314812
DOI: 10.3791/62629 -
Journal of Cancer Research and Clinical... Jan 2023Retinoblastoma (RB) is the most common childhood tumor that can occur in the retina and develop in a sporadic or heritable form. Although various traditional treatment... (Review)
Review
INTRODUCTION
Retinoblastoma (RB) is the most common childhood tumor that can occur in the retina and develop in a sporadic or heritable form. Although various traditional treatment options have been used for patients with RB, identifying novel strategies for childhood cancers is necessary.
MATERIAL AND METHODS
Recently, molecular-based targeted therapies have opened a greater therapeutic window for RB. Long non-coding RNAs (lncRNAs) presented a potential role as a biomarker for the detection of RB in various stages.
CONCLUSION
LncRNAs by targeting several miRNA/transcription factors play critical roles in the stimulation or suppression of RB. In this review, we summarized recent progress on the functions of tumor suppressors or oncogenes lncRNAs in RB.
Topics: Humans; Child; Retinoblastoma; RNA, Long Noncoding; MicroRNAs; Biomarkers; Retinal Neoplasms
PubMed: 36305946
DOI: 10.1007/s00432-022-04398-z -
Clinical & Experimental Ophthalmology Apr 2024In the current era of global health awareness for retinoblastoma (RB), the challenge that lies ahead of us is providing optimal care for children affected with RB in... (Review)
Review
In the current era of global health awareness for retinoblastoma (RB), the challenge that lies ahead of us is providing optimal care for children affected with RB in underdeveloped nations. The understanding of similarities and disparities between various nations across the world aids in achieving comparable outcomes. With dissolving geographic barriers and evolving collaboration, global collaborative studies on RB are becoming increasingly common. They provide real-world, robust evidence on several aspects of RB. This review discusses insights gained from global RB studies regarding the demographics, certain aspects of etiopathogenesis and epidemiology, international travel burden, disparities in clinical presentations based on national income levels, management protocols, pathology, treatment outcomes, and the effect of COVID-19 on RB care across the world. These insights are likely to impact individual practice as well as inform policy reforms.
Topics: Child; Humans; Retinoblastoma; Retinal Neoplasms; Treatment Outcome
PubMed: 38263682
DOI: 10.1111/ceo.14357