Special Issue of Cancers: “Retinoblastoma: Current Challenges and Promising New Approaches”
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- Historically, the discovery of RB1 and the recessive nature of its mutations led to the prototypic description of anti-oncogenes or tumor suppressor genes [1].
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- Behind its role in retinoblastoma tumorigenesis, the protein encoded by the RB1, pRB, belongs to the regulatory INK4A/Cyclin D1/pRB/E2F pathway, universally disrupted in human cancer [2].
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- Retinoblastoma is the only pediatric cancer which presents with recognizable signs, allowing awareness campaigns to be credited with significant shortening of the length of time to diagnosis [3]. As such, retinoblastoma was selected as one of the six pediatric cancers which are priorities of the World Health Organization (WHO) Global Initiative for Childhood Cancer (GICC).
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- Retinoblastoma is considered as a clinical success story in pediatric oncology, credited with a 5-year survival rate of 99% in high-income countries, giving it the best prognosis among pediatric cancers [4].
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- For the first time, the management outcome of heritable retinoblastoma has illustrated the selection relaxation effect of therapeutic intervention for a lethal human disorder via an increased frequency of carriers of germline RB1 pathogenic variants after only a few generations [5].
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- The differential diagnosis of pediatric intra-ocular tumors and/or pseudo-tumors (a) in a multicenter prospective observational study of all new diagnoses of pediatric eye tumors over a 5-year period [8], and (b) through the use of magnetic resonance imaging (MRI) features that best differentiate between retinoblastoma and the most common pseudo-retinoblastoma diagnoses [9].
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- Novel genotype–phenotype correlations by means of a new classification for RB1 mutations, based on variants’ predicted effect on pRB, notably resulting in the hypothesis that truncated pRB could have a dominant-negative effect on wild-type pRB in a localization-dependent manner [10].
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- The determination of the latest age at which ophthalmological screening under narcosis can be safely discontinued in familial retinoblastoma [13]. The authors showed that 99% of cases are diagnosed by 3 years and 100% by 4 years of age.
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- Current indications to secondary enucleation in a consensus paper from the European retinoblastoma group (EURbG), which provided information on when to stop conservative management with absolute and relative criteria for the first time [16].
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- The genomic characterization of metastatic retinoblastoma in (a) the largest cohort of patients with extra-ocular relapse [17], expanding the list of biomarkers associated with tumors at risk of relapse, and (b) two patients affected by the rare subtype 2 retinoblastoma linked to MYCN amplification [18] and metastatic disease to the orbit and lymph nodes resistant to classic systemic chemotherapy regimen. This latter study exemplifies the implementation of customized medicine for retinoblastoma, starting with in vitro cell culture derived from the lymph nodes, followed by high-throughput pharmacological screening to finally identify innovative active drug combinations.
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- The role of liquid biopsies in the management of retinoblastoma by two leading groups reporting (a) the first series of RB patients to undergo the prospective cfDNA analysis of aqueous humor at the time of diagnosis and longitudinally throughout therapy, setting the basis for larger prospective studies investigating the prognostic value of specific somatic alterations [19]; and (b) a review on plasma and aqueous humor liquid biopsies and their potential to transform the management of retinoblastoma across the clinical spectrum, from prenatal diagnosis and minimally disseminated disease to late malignant sequalae [20].
Conflicts of Interest
References
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Munier, F.L. Special Issue of Cancers: “Retinoblastoma: Current Challenges and Promising New Approaches”. Cancers 2023, 15, 2293. https://doi.org/10.3390/cancers15082293
Munier FL. Special Issue of Cancers: “Retinoblastoma: Current Challenges and Promising New Approaches”. Cancers. 2023; 15(8):2293. https://doi.org/10.3390/cancers15082293
Chicago/Turabian StyleMunier, Francis L. 2023. "Special Issue of Cancers: “Retinoblastoma: Current Challenges and Promising New Approaches”" Cancers 15, no. 8: 2293. https://doi.org/10.3390/cancers15082293