Orbital relapse of retinoblastoma in patients with high-risk histopathology features

Cicinelli, Maria Vittoria; Kaliki, Swathi

doi:10.1177/2515841419844080

Cited by 6 publications

(7 citation statements)

References 24 publications

(34 reference statements)

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“…Initial regression of the Rb tumor is followed by an orbital relapse [ 27 ] or recurrence of more aggressive chemo-resistant tumors composed of tumor cells with a much higher tumor-initiating ability than the original tumor [ 28 ]. The EMT program through ZEB1 is known to drive cellular mobility and tumor dissemination in other cancer systems [ 29 ]; however, their role in EMT-driven drug resistance in Rb tumors is unknown.…”

Section: Resultsmentioning

confidence: 99%

Enhanced Epithelial-to-Mesenchymal Transition and Chemoresistance in Advanced Retinoblastoma Tumors Is Driven by miR-181a

Babu

Bisht²,

Mallipatna³

et al. 2022

Cancers

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Advanced retinoblastoma (Rb) tumors display high metastatic spread to distant tissues, causing a potent threat to vision and life. Through transcriptomic profiling, we discovered key upregulated genes that belonged to the epithelial–mesenchymal transition (EMT) and chemotherapy resistance pathways in advanced Rb tumors. Through in vitro models, we further showed that Rb null tumor cells under prolonged chemo drug exposure, acquires a metastasis-like phenotype through the EMT program mediated by ZEB1 and SNAI2 and these cells further acquires chemotherapeutic resistance through cathepsin-L- and MDR1-mediated drug efflux mechanisms. Using a miRNA microarray, we identified miR-181a-5p as being significantly reduced in advanced Rb tumors, which was associated with an altered EMT and drug-resistance genes. We showed that enhancing miR-181a-5p levels in Rb null chemo-resistant sublines reduced the ZEB1 and SNAI2 levels and halted the mesenchymal transition switch, further reducing the drug resistance. We thus identified miR-181a-5p as a therapeutically exploitable target for EMT-triggered drug-resistant cancers that halted their invasion and migration and sensitized them to low-dose chemotherapy drugs.

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Section: Resultsmentioning

confidence: 99%

Enhanced Epithelial-to-Mesenchymal Transition and Chemoresistance in Advanced Retinoblastoma Tumors Is Driven by miR-181a

Babu

Bisht²,

Mallipatna³

et al. 2022

Cancers

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show abstract

“…Initial regression of the Rb tumors post treatment is followed by an orbital relapse or recurrence of a more aggressive chemo-resistant tumors composed of tumor cells with a much higher tumor initiating ability than the original tumor (Cicinelli & Kaliki, 2019). EMT program through ZEB1 is known to drive cellular mobility and tumor dissemination in other types of cancer (Drapela et al, 2020), however their role in EMT driven drug resistance in Rb tumors are unknown.…”

Section: Resultsmentioning

confidence: 99%

Enhanced epithelial to mesenchymal transition and chemoresistance in advanced Retinoblastoma tumors is driven by miR-181a

Babu

Bisht

Mallipatna

et al. 2022

Preprint

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Advanced retinoblastoma (Rb) tumors can infiltrate distant tissues and cause a potent threat to vision and life. Through transcriptomic profiling, we discovered key epithelial to mesenchymal transition (EMT) and chemotherapy resistance genes at higher expression levels in advanced Rb tumors. Rb-/- tumor cells acquire metastasis-like phenotype through the EMT program that critically contributes to chemoresistance. We demonstrate that prolonged chemo-drug exposure in Rb cells elicits an EMT program through ZEB1 and SNAI2 that further acquires therapeutic resistance through cathepsin L and MDR1 mediated drug efflux mechanisms. Further, 16 significantly differentially expressed miRNAs were identified in patient tumors, of which miR-181a-5p was significantly reduced in advanced Rb tumors and associated with altered EMT and drug resistance genes. Enhancing miR-181a-5p levels in Rb-/- cells and Rb-/- chemo-resistant sublines controls EMT transcription factors ZEB1 and SNAI2 and halts the transition switch, thereby reversing drug resistance. We thus identify miR-181a-5p as a potential therapeutic target for EMT triggered drug-resistant cancers that can halt their invasion and sensitize them to low dose chemotherapy drugs.

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“…focal laser), and in advanced cases, eye enucleation [1,2]. High-risk features for extra-ocular spread include tumor invasion of the post laminar optic nerve, choroid, anterior segment or sclera with relapses occurring typically within two years of diagnosis [1,3,4].…”

Section: To the Editormentioning

confidence: 99%

Unusual Clinical Behavior of a Very Late Retinoblastoma Relapse in a Patient with a Germline RB Mutation

Persaud

Seddiq

et al. 2022

Preprint

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Retinoblastoma is the most common ocular tumor of childhood with cure rates exceeding 95%. Patients with high-risk features typically relapse within 3 years of diagnosis. We report a patient with low-risk bilateral retinoblastoma who suffered systemic relapse after eight years. His disease at first relapse was chemosensitive without PET avidity or bone marrow disease following therapy. Six months later, he experienced an isolated CNS relapse and succumbed to refractory disease. “Oncoseq” exome sequencing confirmed the presence of germline RB mutation among all tissues as well as somatic changes which may provide insights into the biology of relapse and tumor.

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Orbital relapse of retinoblastoma in patients with high-risk histopathology features

Cited by 6 publications

References 24 publications

Enhanced Epithelial-to-Mesenchymal Transition and Chemoresistance in Advanced Retinoblastoma Tumors Is Driven by miR-181a

Enhanced Epithelial-to-Mesenchymal Transition and Chemoresistance in Advanced Retinoblastoma Tumors Is Driven by miR-181a

Enhanced epithelial to mesenchymal transition and chemoresistance in advanced Retinoblastoma tumors is driven by miR-181a

Unusual Clinical Behavior of a Very Late Retinoblastoma Relapse in a Patient with a Germline RB Mutation

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