Related Experiment Video
Updated: Sep 17, 2025
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Gene context drift identifies drug targets to mitigate cancer treatment resistance
Amir Jassim1, Birgit V Nimmervoll1, Sabrina Terranova1
1Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Abstract:
Cancer treatment often fails because combinations of different therapies evoke complex resistance mechanisms that are hard to predict. We introduce REsistance through COntext DRift (RECODR): a computational pipeline that combines co-expression graph networks of single-cell RNA sequencing profiles with a graph-embedding approach to measure changes in gene co-expression context during cancer treatment. RECODR is based on the idea that gene co-expression context, rather than expression level alone, reveals important information about treatment resistance. Analysis of tumors treated in preclinical and clinical trials using RECODR unmasked resistance mechanisms -invisible to existing computational approaches- enabling the design of highly effective combination treatments for mice with choroid plexus carcinoma, and the prediction of potential new treatments for patients with medulloblastoma and triple-negative breast cancer. Thus, RECODR may unravel the complexity of cancer treatment resistance by detecting context-specific changes in gene interactions that determine the resistant phenotype.
Insights
A new computational pipeline, REsistance through COntext DRift (RECODR), identifies cancer treatment resistance by analyzing gene co-expression context. This approach reveals hidden resistance mechanisms, aiding in designing more effective combination therapies.
Area of Science:
- Computational biology
- Genomics
- Cancer research
Background:
- Cancer treatment failure is often due to unpredictable resistance mechanisms.
- Existing computational approaches struggle to identify complex resistance patterns.
Purpose of the Study:
- To introduce REsistance through COntext DRift (RECODR), a novel computational pipeline.
- To leverage gene co-expression context for predicting and understanding cancer treatment resistance.
Main Methods:
- Utilizing single-cell RNA sequencing profiles.
- Building co-expression graph networks.
- Applying a graph-embedding approach to measure changes in gene co-expression context.
Main Results:
- RECODR identified resistance mechanisms previously undetectable by other methods.
- Successfully designed effective combination treatments for preclinical models (choroid plexus carcinoma).
- Predicted potential new treatments for medulloblastoma and triple-negative breast cancer.
Conclusions:
- RECODR effectively unravels the complexity of cancer treatment resistance.
- Detecting context-specific gene interaction changes is key to understanding the resistant phenotype.
- This pipeline offers a promising tool for developing improved combination cancer therapies.
More Related Videos
08:59Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
Published on: December 11, 2017
08:52Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Related Concept Videos
02:56Treatment Resistant Cancers
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:26Targets for Drug Action: Overview
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
02:40Cancer Stem Cells and Tumor Maintenance
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...