Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

A Genome-Forward Approach to Tackling Drug-Resistant Cancers

Published: Thursday, September 26, 2013
Last Updated: Thursday, September 26, 2013
Bookmark and Share
If you really want to understand why a particular human cancer resists treatment, you have to be able to study that tumor in a way that just isn't possible in humans.

Cancer biologists have been developing a new approach to this challenge, by transplanting human cancers directly from patients to mice whose crippled immune systems will allow those human tissues to grow. According to research published in the Cell Press publication Cell Reports on September 19th, this new approach permits analysis of human cancer in unprecedented detail. The new work shows that those transplanted cancers, known as PDX (for patient-derived xenografts), are very good genomic replicas of the original at every level of analysis.

Overall, the PDX approach promises to speed the development of new drugs along with doctors' ability to make more precise choices about how those drugs are used to treat patients, the researchers say.

"The development of precision pharmacology is clearly the current focus in PDX research," said Matthew Ellis of Washington University in St Louis. "Human testing is hugely expensive, and often the response rates for the patients on experimental drugs are low because the biology of each patient is not well defined. Panels of clinically and genomically annotated PDX can therefore be very valuable for studying drug action and developing predictive biomarkers. Extensive pre- and post-drug sampling can be conducted to study drug effects and drug resistance in a way that would be impossible in the clinical setting."

In the new study, Ellis and his team transplanted drug-resistant human breast cancers into mice and then made very detailed comparisons of those transplanted tumors versus the originals.

The researchers' deep whole-genome analyses showed a high degree of genomic fidelity. In other words, the complex human tumor tissues in the mice looked very much like those in the people they originally came from. While some new mutations did arise after transplantation, those genetic changes rarely had functional significance.

The researchers were surprised to discover that the original and PDX cancers were similar at the cellular level as well. Cancer cells carrying mutations that were relatively rare in the patient were also maintained at lower frequencies in the mice. Likewise, more dominant clones in the original tumor tended to stay dominant in the mice. This suggests that the frequency of genetically distinct tumor cells is in an equilibrium that survives transplantation into mice for reasons that aren't yet clear.

An analysis of multiple estrogen receptor-positive PDX from patients with endocrine therapy-resistant disease shows just how this approach can yield tumor-specific explanations for therapy resistance. Resistant tumors were associated with different kinds of alterations to the estrogen receptor gene ESR1, the researchers found, producing different responses to endocrine therapy.

"The prevalence of ESR1 mutations and gene arrangements in the luminal PDX was a deep surprise to me as I thought these events were rare," Ellis said. "There had been very sporadic reports of ESR1 point mutations in clinical samples over the years, but to find them at high prevalence in the PDX and therefore in a setting where the link to endocrine therapy resistance can be directly studied was, for me, a critical breakthrough in our understanding of this critical problem."


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Fountain-of-Youth Gene Repairs Tissue Damage in Adults
Young animals recover from tissue damage better than adults, and from Charles Darwin's time until now, scientists have puzzled over why this is the case.
Monday, November 11, 2013
Scientific News
Long Telomeres Associated with Increased Lung Cancer Risk
Genetic predisposition for long telomeres predicts increased lung adenocarcinoma risk.
Expanding the Brain
A team of researchers has identified more than 40 new “imprinted” genes, in which either the maternal or paternal copy of a gene is expressed while the other is silenced.
Identifying a Key Growth Factor in Cell Proliferation
Researchers discover that aspartate is a limiter of cell proliferation.
Study Uncovers Target for Preventing Huntington’s Disease
Scientists from Cardiff University believe that a treatment to prevent or delay the symptoms of Huntington’s disease could now be much closer, following a major breakthrough.
The Genetic Roots of Adolescent Scoliosis
Scientists at the RIKEN Center for Integrative Medical Sciences in collaboration with Keio University in Japan have discovered a gene that is linked to susceptibility of Scoliosis.
A Gene-Sequence Swap Using CRISPR to Cure Haemophilia
For the first time chromosomal defects responsible for hemophilia have been corrected in patient-specific iPSCs using CRISPR-Cas9 nucleases
New Tool Uses 'Drug Spillover' to Match Cancer Patients with Treatments
Researchers have developed a new tool that improves the ability to match drugs to disease: the Kinase Addiction Ranker (KAR) predicts what genetics are truly driving the cancer in any population of cells and chooses the best "kinase inhibitor" to silence these dangerous genetic causes of disease.
Understanding the Molecular Origin of Epigenetic Markers
Researchers at IRB Barcelona discover the molecular mechanism that determines how epigenetic markers influence gene expression.
New Tech Enables Epigenomic Analysis with a Mere 100 Cells
A new technology that will dramatically enhance investigations of epigenomes, the machinery that turns on and off genes and a very prominent field of study in diseases such as stem cell differentiation, inflammation and cancer has been developed by researchers at Virginia Tech.
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!