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MicroRNAs in Cancer: A Historical Perspective on the Path from Discovery to Therapy.

ABSTRACT: Recent progress in microRNA (miRNA) therapeutics has been strongly dependent on multiple seminal discoveries in the area of miRNA biology during the past two decades. In this review, we focus on the historical discoveries that collectively led to transitioning miRNAs into the clinic. We highlight the pivotal studies that identified the first miRNAs in Caenorhabditis elegans to the more recent reports that have fueled the quest to understand the use of miRNAs as markers for cancer diagnosis and prognosis. In addition, we provide insights as to how unraveling basic miRNA biology has provided a solid foundation for advancing miRNAs, such as miR-34a, therapeutically. We conclude with a brief examination of the current challenges that still need to be addressed to accelerate the path of miRNAs to the clinic: including delivery vehicles, miRNA- and delivery-associated toxicity, dosage, and off target effects.

SUBMITTER: Orellana EA

PROVIDER: S-EPMC4586775 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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MicroRNAs in Cancer: A Historical Perspective on the Path from Discovery to Therapy.

Orellana Esteban A EA Kasinski Andrea L AL

Cancers 20150727 3

Recent progress in microRNA (miRNA) therapeutics has been strongly dependent on multiple seminal discoveries in the area of miRNA biology during the past two decades. In this review, we focus on the historical discoveries that collectively led to transitioning miRNAs into the clinic. We highlight the pivotal studies that identified the first miRNAs in Caenorhabditis elegans to the more recent reports that have fueled the quest to understand the use of miRNAs as markers for cancer diagnosis and p ...[more]

PMID: 26226002

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Project description:This review describes the clinical and basic research that led to the description of Flammer syndrome. It is narrated from a personal perspective. This research was initiated by the observation of an increased long-term fluctuation of visual fields in a subgroup of glaucoma patients. As these patients had strikingly cold hands, peripheral blood flow was tested with a capillary microscopy, and vasospastic syndrome (VS) was diagnosed. Further studies on these patients revealed frequently weakened autoregulation of ocular blood flow and increased flow resistivity in retroocular vessels. Their retinal vessels were more rigid and irregular and responded less to flickering light. Holistic investigation demonstrated low blood pressure, silent myocardial ischaemia, altered beat-to-beat variation, altered gene expression in the lymphocytes, slightly increased plasma endothelin level and increased systemic oxidative stress. This combination of signs and symptoms was better described by the term primary vascular dysregulation (PVD) than by VS. Subsequent studies showed additional symptoms frequently related to PVD, such as low body mass index, cold extremities combined with slightly increased core temperature, prolonged sleep onset time, reduced feelings of thirst, increased sensitivity to smell and also for certain drugs and increased retinal venous pressure. To better characterise this entire syndrome, the term Flammer syndrome (FS) was introduced. Most subjects with FS were healthy. Nevertheless, FS seemed to increase the risk for certain eye diseases, particularly in younger patients. This included normal-tension glaucoma, anterior ischaemic optic neuropathy, retinal vein occlusions, Susac syndrome and central serous chorioretinopathy. Hereditary diseases, such as Leber's optic neuropathy or retinitis pigmentosa, were also associated with FS, and FS symptoms and sings occurred more frequent in patients with multiple sclerosis or with acute hearing loss. Further research should lead to a more concise definition of FS, a precise diagnosis and tools for recognizing people at risk for associated diseases. This may ultimately lead to more efficient and more personalised treatment.

Dataset Information

MicroRNAs in Cancer: A Historical Perspective on the Path from Discovery to Therapy.

Publications

MicroRNAs in Cancer: A Historical Perspective on the Path from Discovery to Therapy.

Similar Datasets

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