Abstract
Introduction:
Emerging evidence demonstrates that the high mobility group A1 (HMGA1) chromatin remodeling protein is a key molecular switch required by cancer cells for tumor progression and a poorly differentiated, stem-like state. Because the HMGA1 gene and proteins are expressed at high levels in all aggressive tumors studied to date, research is needed to determine how to 'turn off' this master regulatory switch in cancer.
Areas covered:
In this review, we describe prior studies that underscore the central role of HMGA1 in refractory cancers and we discuss approaches to target HMGA1 in cancer therapy.
Expert opinion:
Given the widespread overexpression of HMGA1 in diverse, aggressive tumors, further research to develop technology to target HMGA1 holds immense promise as potent anticancer therapy. Previous work in preclinical models indicates that delivery of short hairpin RNA or interfering RNA molecules to 'switch off' HMGA1 expression dramatically impairs cancer cell growth and tumor progression. The advent of nanoparticle technology to systemically deliver DNA or RNA molecules to tumors brings this approach even closer to clinical applications, although further efforts are needed to translate these advances into therapies for cancer patients.
MeSH terms
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Animals
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Antibiotics, Antineoplastic / pharmacology
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Antibiotics, Antineoplastic / therapeutic use
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Cell Differentiation
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Chromatin / ultrastructure
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Clinical Trials as Topic
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Cyclooxygenase 2 Inhibitors / pharmacology
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Cyclooxygenase 2 Inhibitors / therapeutic use
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Disease Progression
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Drug Screening Assays, Antitumor
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Flavonoids / pharmacology
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Flavonoids / therapeutic use
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Gene Expression Regulation, Neoplastic / drug effects
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Genetic Therapy
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HMGA1a Protein / antagonists & inhibitors*
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HMGA1a Protein / genetics
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HMGA1a Protein / physiology
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HMGA1b Protein / antagonists & inhibitors*
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HMGA1b Protein / genetics
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HMGA1b Protein / physiology
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Humans
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Mice
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Molecular Targeted Therapy / methods*
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Nanoparticles / administration & dosage
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Neoplasm Invasiveness / physiopathology
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Neoplasm Proteins / antagonists & inhibitors*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology
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Neoplasms / drug therapy
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Oxazines / pharmacology
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Oxazines / therapeutic use
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Piperidines / pharmacology
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Piperidines / therapeutic use
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RNA, Small Interfering / administration & dosage
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RNA, Small Interfering / pharmacology
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RNA, Small Interfering / therapeutic use
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Stem Cells / cytology
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Stem Cells / drug effects
Substances
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Antibiotics, Antineoplastic
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Antineoplastic Agents
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Chromatin
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Cyclooxygenase 2 Inhibitors
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Flavonoids
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Neoplasm Proteins
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Oxazines
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Piperidines
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RNA, Small Interfering
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FR 900482
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FK 973
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HMGA1b Protein
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HMGA1a Protein
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alvocidib