Navigation Links
Scientists identify overactive genes in aggressive breast cancers
Date:6/1/2011

BOSTONScientists at Dana-Farber Cancer Institute have identified an overactive network of growth-spurring genes that drive stem-like breast cancer cells enriched in triple-negative breast tumors, a typically aggressive cancer that is highly resistant to current therapies.

Kornelia Polyak, MD, PhD, a breast cancer geneticist at Dana-Farber, and colleagues found that a large proportion of cells within these tumors showed elevated activity in a network of genes called the Jak2/Stat3 pathway. Experiments have demonstrated that a drug specifically aimed to block this pathway halted the growth of such tumors in mice. The report will be published online June 1 by The Journal of Clinical Investigation in advance of its July print issue.

Polyak called the strategy very promising. "The discovery of these targets will rapidly lead to clinical trials with the hope of achieving one of the first specific therapies for triple-negative breast cancers," said Polyak, senior author of the findings that was submitted by a large collaboration of scientists.

Jak2/Stat3 inhibitors are already in advanced phases of clinical testing for certain blood cancers that are driven by the Jak2/Stat3 pathway. Polyak noted that because these inhibitors have already been tested in humans and appear to be relatively non-toxic, it should be possible to begin testing them in breast cancer patients soon.

Triple-negative breast cancers are characterized by a lack of estrogen, progesterone, and HER2 receptors, which makes them unresponsive to targeted treatments that block those receptors. These tumors, also termed "basal-like," make up an estimated 15 to 20 percent of breast cancers and tend to occur in younger women, those with BRCA1 gene mutations, and black women.

Polyak previously found that triple-negative tumors typically contain a large number of "stem-like" breast cancer cells, labeled CD44+CD24- cells, referring to identifying markers on their surfaces. They resemble stem cells, as they constantly renew themselves and make tumors likely to spread to distant organs.

As a result, Polyak and colleagues believe that new treatments aimed at specifically knocking out these CD44+CD24- cells with activated Jak2/Stat3 signaling could be useful in combating triple-negative cancers and potentially other tumors that contain these cells.

The investigators surveyed genes present in CD44+CD24- cells and found 1,576 genes that differed from those in other, more differentiated epithelial cancer cells within tumors. Additional experiments assessing the viability of CD44+CD24- cells when each of these genes was inhibited individually narrowed the field to 15 genes that were required for their growth and thus looked like promising targets for selective drugs. These 15 genes were linked to the overactive Jak2/Stat3 pathway, which in turn was triggered by a growth factor signal, interleukin-6, or IL-6.

When the activity of several of those genes was blocked in CD44+/CD24- tumor cells, the level of Stat3 signaling was reduced and cell growth was suppressed, the researchers said.

Polyak said that inhibitor drugs exist for five of the genes identified in the CD44+CD24- cell network, and two of those drugs are currently in advanced clinical testing.

Nancy Lin, MD, a Dana-Farber oncologist who will lead the clinical trial of a Jak2/Stat3 inhibitor in breast cancer patients, said women who volunteer for the trial will be tested to determine whether the pathway is abnormally activated in their cancer. Those who test positive will be candidates for treatment with the drug. According to Lin, the abnormal pathway is expected to be found in 50 to 60 percent of patients with triple-negative cancers.


'/>"/>

Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
Source:Eurekalert  

Related medicine news :

1. Scientists Pinpoint Area of Brain That Fears Losing Money
2. Scientists Discover How HIV Is Transmitted Between Men
3. Prevention Is Key Research Goal for Premature Babies, Scientists Say
4. Scientists Discover Molecular Pathway for Organ Tissue Regeneration and Repair
5. Scientists find donut-shaped structure of enzyme involved in energy metabolism
6. Neuroscientists reveal new links that regulate brain electrical activity
7. Two UCSF Scientists to Receive Prestigious Dementia Research Honor
8. Johns Hopkins scientists develop personalized blood tests for cancer using whole genome sequencing
9. Scientists Spot Genetic Fingerprints of Individual Cancers
10. Scientists Unravel Mysteries of Intelligence
11. MSU scientists develop more effective method of predicting lead-poisoning risk
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Scientists identify overactive genes in aggressive breast cancers
(Date:3/29/2017)... MD (PRWEB) , ... March 30, 2017 , ... CHARM ... Charm City Run has announced that Mercy Medical Center will serve as the official ... the Mid-Atlantic region. On Sunday, June 25, 2017, thousands of women will walk or ...
(Date:3/29/2017)... ... 30, 2017 , ... Sublime Naturals and its founder, Kathy Heshelow, are big ... has been used for thousands of years. , "The West has caught on, and ... Turmeric: How to Use it For Your Wellness. Overcome Inflammation, Enemy of the Body. ...
(Date:3/29/2017)... Wellington, Florida (PRWEB) , ... March 29, 2017 ... ... will be hosting several educational opportunities for attending prescribers at the upcoming World ... Pharmacy Network said, “A4M has always been recognized as the visionary leader in ...
(Date:3/29/2017)... ... March 29, 2017 , ... The Wall Centre Dental ... new patients from Burnaby, BC. Patients in need of experienced orthodontics, laser dentistry, ... see the esteemed team at Wall Centre Dental. Drs. Parviz Roshan, Siamak Tehrani, ...
(Date:3/29/2017)... ... March 29, 2017 , ... Patients interested ... Carnegie, OK, from Dr. Jamie Cameron, with or without a referral. The FASTBRACES ... orthodontic treatment. Depending on each patient’s case, treatment with the FASTBRACES system could ...
Breaking Medicine News(10 mins):
(Date:3/29/2017)... New York , March 29, 2017 /PRNewswire/ ... recently published a report, which provides an exhaustive ... to the study, nearly 242 companies are functional ... fragmented and competitive. With the leading companies, such ... Purdue Pharma LP, focusing aggressively on various marketing ...
(Date:3/29/2017)... Research and Markets has announced the addition of the ... ... drugs market to grow at a CAGR of 2.87% during the ... 2017-2021, has been prepared based on an in-depth market analysis with ... its growth prospects over the coming years. The report also includes ...
(Date:3/29/2017)... March 29, 2017 Varian Medical Systems (NYSE: ... for the second quarter of fiscal year 2017 following the ... news release will be followed by a teleconference available to ... and a link to the conference call webcast will be ... access the teleconference call and replay: ...
Breaking Medicine Technology: