Restoring expression of miR-16: a novel approach to therapy for malignant pleural mesothelioma

Reid, Glen; Pel, Marcella; Kirschner, Michaela B.; Cheng, Yuen Yee; Mugridge, Nancy; Weiss, Jocelyn; Williams, Marissa; Wright, Casey M.; Edelman, James; Vallely, Michael P.; McCaughan, Brian C.; Klebe, Sonja; Brahmbhatt, Himanshu; MacDiarmid, Jennifer; Zandwijk, Nico van

doi:10.1093/annonc/mdt412

Cited by 228 publications

(236 citation statements)

References 25 publications

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“…32,33 Another study showed that miR-15/16 expression is downregulated in malignant pleural mesothelioma (MPM). 34 Administration of synthetic mimics to restore miR-15/16 expression led to growth inhibition in MPM cell lines and in xenograft-bearing nude mice; administration of miR-15/16 mimics led to consistent inhibition of MPM tumor growth. 34 …”

Section: Mir-15/16 At 13q14 Gene Discoverymentioning

confidence: 95%

Role of miR-15/16 in CLL

2014

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B-cell chronic lymphocytic leukemia (CLL) is the most common adult leukemia. The most common chromosomal abnormalities detectable by cytogenetics include deletion at 13q (55%), 11q (18%), trisomy 12 (12-16%) and 17p (8%). In 2002, we discovered that a microRNA cluster miR-15a/miR-16-1 (miR-15/16) is the target of 13q deletions in CLL. MicroRNAs encoded by the miR-15/16 locus (miR-15 and miR-16) function as tumor suppressors. Expression of these miRNAs downregulated in CLL, melanoma, colorectal cancer, bladder cancer and other solid tumors. miR-15/16 cluster targets multiple oncogenes, including BCL2, Cyclin D1, MCL1 and others. The most important target of miR-15/16 in CLL is arguably BCL2, as BCL2 is overexpressed in almost all CLLs. In this review, we discuss the discovery, functions, clinical relevance and treatment opportunities related to miR-15/16.

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Section: Mir-15/16 At 13q14 Gene Discoverymentioning

confidence: 95%

Role of miR-15/16 in CLL

2014

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“…Miravirsen is a miR-122 antagonist used for the treatment of Hepatitis C virus infection 52 and TargoMiR, a miR-16 mimic, has been used in patients with recurrent malignant pleural mesothelioma (MPM) and advanced non-small cell lung cancer (NSCLC), delivered intavenously with epidermal growth factor receptor (EGFR)-targeted minicells. [53][54][55] A variety of nanoparticle-based delivery methods have been developed for the robust and safe delivery of siRNA and miRNA payloads, including inorganic, polymer or lipid-based nanoparticles. 2,56 A silica-based nanoparticle conjugated with a disialoganglioside GD2 antibody as targeting moiety was used to express miR-34a in neuroblastoma, which reduced tumor growth and vascularization by decreasing the levels of N-myc and increasing tissue inhibitor of metallopeptidase 2 (TIMP2).…”

Section: Mir-182 Expression Influences Multiple Tumor Biological Propmentioning

confidence: 99%

miRNA-182 and the regulation of the glioblastoma phenotype - toward miRNA-based precision therapeutics

2015

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“…[121][122][123] A therapeutic approach to restoring mir-15/mir-16 expression termed targomirs is an approach comprised of a combination of mir-15/mir-16 mimetic drugs encapsulated in a bacterial cellderived system, coated with an epidermal growth factor receptor-targeting antibody. 124 Infusions of targomirs were associated with a steep rise in inflammatory cytokines and elevations in liver enzymes; however, these were transient, and several patients reported improved quality of life while on treatment.…”

Section: Clinical Experience With Mirna Modulatorsmentioning

confidence: 99%

“…124 Infusions of targomirs were associated with a steep rise in inflammatory cytokines and elevations in liver enzymes; however, these were transient, and several patients reported improved quality of life while on treatment. 123,124 microRNA-modulating drugs are an exciting class of RNA therapeutics as individual miRNAs regulate the expression of multiple important biological pathways. It will be exciting to see how this new class of drugs evolves as cancer therapeutics.…”

Section: Clinical Experience With Mirna Modulatorsmentioning

confidence: 99%

RNA Therapeutics in Oncology: Advances, Challenges, and Future Directions

MacLeod

Crooke

2017

The Journal of Clinical Pharma

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RNA-based therapeutic technologies represent a rapidly expanding class of therapeutic opportunities with the power to modulate cellular biology in ways never before possible. With RNA-targeted therapeutics, inhibitors of previously undruggable proteins, gene expression modulators, and even therapeutic proteins can be rationally designed based on sequence information alone, something that is not possible with other therapeutic modalities. The most advanced RNA therapeutic modalities are antisense oligonucleotides (ASOs) and small interfering RNAs. Particularly with ASOs, recent clinical data have demonstrated proof of mechanism and clinical benefit with these approaches across several nononcology disease areas by multiple routes of administration. In cancer, next-generation ASOs have recently demonstrated single-agent activity in patients with highly refractory cancers. Here we discuss advances in RNA therapeutics for the treatment of cancer and the challenges that remain to solidify these as mainstay therapeutic modalities to bridge the pharmacogenomic divide that remains in cancer drug discovery.

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Restoring expression of miR-16: a novel approach to therapy for malignant pleural mesothelioma

Cited by 228 publications

References 25 publications

Role of miR-15/16 in CLL

Role of miR-15/16 in CLL

miRNA-182 and the regulation of the glioblastoma phenotype - toward miRNA-based precision therapeutics

RNA Therapeutics in Oncology: Advances, Challenges, and Future Directions

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