We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us

Download Mobile App




Targeting MicroRNA Blocks Drug Tolerance in Some Cancers

By LabMedica International staff writers
Posted on 15 Apr 2019
Cancer researchers have suggested that by exploiting the link between a specific microRNA and the tricarboxylic acid energy-producing cycle it may be possible to prevent or reverse the development of drug tolerance or resistance by non-small-cell lung carcinomas.

MicroRNAs (miRNAs) and short interfering RNAs (siRNA) comprise a class of about 20 nucleotides-long RNA fragments that block gene expression by attaching to molecules of messenger RNA in a fashion that prevents them from transmitting the protein synthesizing instructions they had received from the DNA. More...
MiRNAs resemble siRNAs of the RNA interference (RNAi) pathway, except miRNAs derive from regions of RNA transcripts that fold back on themselves to form short hairpins, whereas siRNAs derive from longer regions of double-stranded RNA. With their capacity to fine-tune protein expression via sequence-specific interactions, miRNAs help regulate cell maintenance and differentiation.

Non-small cell lung cancers, which comprise about 85% of lung cancer diagnoses, tend to be less aggressive but harder to treat than small cell lung cancers. About 10% of non-small-cell lung carcinomas carry an epidermal growth factor receptor (EGFR) mutation. Drug tolerance developed by cancer cells is an acute defense response preceding a fully drug-resistant state and tumor relapse; however, there are few therapeutic agents targeting drug tolerance in the clinic.

As part of their effort to identify drugs able to modify drug tolerance, investigators at Beth Israel Deaconess Medical Center (Boston, MA, USA) found that the microRNA miR-147b initiated a reversible state of tolerance to the epidermal growth factor receptor (EGFR) inhibitor osimertinib in non-small-cell lung cancer. Osimertinib is a medication used to treat non-small-cell lung carcinomas with the specific EGFR mutation. It is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor.

The investigators reported in the April 8, 2019, online edition of the journal Nature Metabolism that using miRNA-seq analysis, they determined that miR-147b was the most upregulated microRNA in osimertinib-tolerant and EGFR-mutated lung cancer cells. Whole-transcriptome analysis of single-cell-derived clones revealed a link between osimertinib tolerance and pseudohypoxia responses irrespective of oxygen levels.

Further metabolomics and genetic studies demonstrated that osimertinib tolerance was driven by miR-147b-mediated repression of VHL (von Hippel-Lindau tumor suppressor) and succinate dehydrogenase, which are linked to the tricarboxylic acid energy-producing cycle and pseudohypoxia pathways. Finally, pretreatment with a miR-147b inhibitor delayed osimertinib-associated drug tolerance in patient-derived three-dimensional structures.

"These results were a surprise and represent a total novel finding in the area," said senior author Dr. Frank J. Slack, professor of medical research at Beth Israel Deaconess Medical Center. "In this study, we discovered that a microRNA known as miR-147b is a critical mediator of resistance among a subpopulation of tumor cells that adopt a tolerance strategy to defend against EGFR-based anticancer treatments. We are currently testing the idea of targeting this new pathway as a therapy in clinically relevant mouse models of EGFR-mutant lung cancer."

Related Links:
Beth Israel Deaconess Medical Center


Gold Member
Quantitative POC Immunoassay Analyzer
EASY READER+
POC Helicobacter Pylori Test Kit
Hepy Urease Test
New
HBV DNA Test
GENERIC HBV VIRAL LOAD VER 2.0
New
Sperm Quality Analyis Kit
QwikCheck Beads Precision and Linearity Kit
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








Channels

Hematology

view channel
Image: The microfluidic device for passive separation of platelet-rich plasma from whole blood (Photo courtesy of University of the Basque Country)

Portable and Disposable Device Obtains Platelet-Rich Plasma Without Complex Equipment

Platelet-rich plasma (PRP) plays a crucial role in regenerative medicine due to its ability to accelerate healing and repair tissue. However, obtaining PRP traditionally requires expensive centrifugation... Read more

Immunology

view channel
Image: An innovative deep learning model can accurately predict MSI tumor and immune checkpoint inhibitor responsiveness (Photo courtesy of Jae-Ho Cheong/Yonsei University College of Medicine)

AI Model Accurately Predicts MSI Tumor and Immune Checkpoint Inhibitor Responsiveness

One in three people is expected to develop cancer in their lifetime, and a key factor in patient prognosis is the tumor’s microsatellite status—whether it is stable or shows microsatellite instability-high (MSI-H).... Read more

Pathology

view channel
Image: Virtual staining of label-free tissue in imaging mass spectrometry (Photo courtesy of Ozcan Lab/UCLA)

Deep Learning Advances Imaging Mass Spectrometry with Virtual Histological Detail

Imaging mass spectrometry (IMS) is a powerful technique that can map thousands of molecular species in biological tissues with exceptional chemical specificity. However, IMS is hindered by relatively low... Read more

Industry

view channel
Image: Alzheimer’s Association has released its first clinical practice guideline for blood-based biomarker tests (Photo courtesy of Alzheimer’s Association)

New Clinical Guidelines Recommend Use of Blood Tests Instead of Brain Scans for Alzheimer’s Diagnosis

Alzheimer’s disease is a progressive neurodegenerative condition that remains challenging to diagnose early and accurately, particularly in individuals with cognitive impairment. Despite the availability... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.