Featured Research

from universities, journals, and other organizations

A genome-forward approach to tackling drug-resistant cancers

Date:
September 19, 2013
Source:
Cell Press
Summary:
A new approach to tackling drug-resistant cancers 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.

If you really want to understand why a particular human cancer resists treatment, you have to be able to study that tumor -- really study it -- 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.

Related Articles


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."


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Journal Reference:

  1. Li S, et al. Endocrine therapy resistant ESR1 variants revealed by genomic characterization of breast cancer derived xenografts. Cell Reports, September 19, 2013

Cite This Page:

Cell Press. "A genome-forward approach to tackling drug-resistant cancers." ScienceDaily. ScienceDaily, 19 September 2013. <www.sciencedaily.com/releases/2013/09/130919122256.htm>.
Cell Press. (2013, September 19). A genome-forward approach to tackling drug-resistant cancers. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2013/09/130919122256.htm
Cell Press. "A genome-forward approach to tackling drug-resistant cancers." ScienceDaily. www.sciencedaily.com/releases/2013/09/130919122256.htm (accessed December 19, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, December 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins