Navigation Links
PI3K/mTOR pathway proteins tied to poor prognosis in breast cancer

CHICAGO - Four proteins involved in translation, the final step of general protein production, are associated with poor prognosis in hormone-receptor-positive breast cancer when they are dysregulated, researchers reported at the AACR Annual Meeting 2012.

All of the aberrantly activated translational proteins are regulated by the PI3K/mTOR molecular signaling pathway, which has been implicated in development and progression of several cancers.

More recently, mTOR activation has been tied to resistance to standard endocrine therapy in estrogen-receptor positive breast cancer, said Funda Meric-Bernstam, M.D., professor in MD Anderson's Department of Surgical Oncology, who presented the research at AACR.

"These data underline the importance of the PI3K/mTOR pathway in hormone receptor-positive breast cancer and suggest potential new prognostic factors and therapeutic targets," said Meric-Bernstam, who also is medical director of MD Anderson's Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy.

Two drugs that inhibit mTOR, everolimus and temsirolimus, are approved for treatment of certain cancers and there are dozens of other agents in clinical trials, she said.

Cancer cells rely on increased protein synthesis

Genes express messenger RNA, which is in turn processed through a cell's ribosomes to produce a specific protein, a step called translation.

"Cancer cells need a lot of protein synthesis to grow and survive," Meric-Bernstam said. She and colleagues systematically analyzed several major translation-regulating proteins in tumors from 190 patients with stage 1 to stage 3 hormone receptor-positive breast cancer. Median follow-up was 96 months.

They found four aberrations that were predictors of overall survival. They remained significant even after multivariable analysis accounting for other factors such as age and node-positive status that also affect survival. They are:

  • Increased phosphorylation of ribosomal protein S6 (pS6) and of translation initiation factor 4E-binding protein 1 (p4E-BP1).
  • Increased expression of eukaryotic elongation factor 2 kinase (eEF2K).
  • Decreased expression of programmed cell death protein 4 (pdcd4).

Their findings, if validated by additional studies, could lead to markers that help select patients who may have a high risk of relapse if treated with traditional endocrine therapy alone and identify those who might benefit from an additional targeted therapy, Meric-Bernstam noted.

Results from a major phase III clinical trial presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium showed that the mTOR inhibitor everolimus increased progression-free survival when combined with the hormonal therapy exemestane to treat resistant hormone receptor-positive breast cancer.

"As we understand how to select patients better we'll be able to more efficiently use these targeted therapies to improve outcomes for breast cancer patients," Meric-Bernstam said.


Contact: Scott Merville
University of Texas M. D. Anderson Cancer Center

Related medicine news :

1. Scientists link 2 cancer-promoting pathways in esophageal cancer
2. Pancreatic Cancer Action Network-AACR Pathway to Leadership grants
3. PCP genetic pathway acts as stop sign for cell growth
4. New pathway found for regulation of blood vessel growth in cancer
5. Boston University research suggests new pathways for cancer progression
6. Possible new pathway can overcome glioblastoma resistance
7. Plant flavonoid luteolin blocks cell signaling pathways in colon cancer cells
8. TGen researchers map potential genetic origins, pathways of lung cancer in nonsmokers
9. MS May Take a Different Pathway Than Previously Thought
10. Traumatic injury sets off a genomic storm in immune system pathways
11. New gene study of ADHD points to defects in brain signaling pathways
Post Your Comments:
(Date:11/27/2015)... ... November 27, 2015 , ... CBD College is proud to ... Programs (CAAHEP) awarded accreditation to its Diagnostic Medical Sonography program. CBD College is honored ... one of twelve colleges and universities in the state of California make the cut. ...
(Date:11/26/2015)... ... November 26, 2015 , ... Patients ... central Michigan, have come together on Thanksgiving Day to share the things that ... viewing on the Serenity Point YouTube channel, patients displayed what they wrote on ...
(Date:11/26/2015)... ... ... Jobs in hospital medical laboratories and in the imaging field lead the ... Aureus Medical Group . These fields, as well as travel nursing, ranked ... jobs through the company’s website, , The leading healthcare staffing agency ...
(Date:11/26/2015)... ... ... Indosoft Inc., developer and distributor of the world-class Asterisk based contact center ... reliability. , The new Q-Suite 6 platform is based on the latest Java Enterprise ... a specific piece of software for many key components of the suite. Much of ...
(Date:11/25/2015)... ... November 25, 2015 , ... ... recognized once again for its stellar workplace culture with the company’s Cincinnati office ... , Medical Solutions’ Cincinnati office was named a finalist in Cincinnati Business Courier’s ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... November 26, 2015 ... "Self Administration of High Viscosity Drugs" report ... has announced the addition of the "Self ... their offering. --> Research and Markets ... the "Self Administration of High Viscosity Drugs" ...
(Date:11/26/2015)... November 26, 2015 ... the "Radioimmunoassay Market by Type (Reagents ... Industry, Academics, Clinical Diagnostic Labs), Application (Research, ... to 2020" report to their offering. ... the addition of the "Radioimmunoassay Market ...
(Date:11/25/2015)... 25, 2015 ... the "Global Brain Monitoring Devices Market ... --> ) has announced the ... Devices Market 2015-2019" report to their ... ( ) has announced the addition ...
Breaking Medicine Technology: