Proteins Associated With Poor Prognosis in Hormone Receptor-positive Breast Cancer Identified
- Activation of protein translation linked to more aggressive node-positive disease.
- Markers identified are regulated by PI3K/mTOR signaling pathway.
CHICAGO — Researchers have identified specific proteins involved in translation that when overexpressed or activated are associated with a poorer prognosis in hormone receptor-positive breast cancer, suggesting their role as prognostic markers and therapeutic targets, according to results presented at the AACR Annual Meeting 2012, held here March 31 – April 4.
“Overexpression or activation of some proteins involved in translation is associated with more aggressive node-positive breast cancers,” said Funda Meric-Bernstam, M.D., professor of surgical oncology at the University of Texas MD Anderson Cancer Center and medical director at the Institute of Personalized Cancer Therapy in Houston, Texas. “The results suggest that translational aberrations play an important role in cancer progression.”
Through analysis of tumors from 190 patients with stage 1 to stage 3 hormone receptor-positive breast cancer, the researchers found that increased phosphorylation of ribosomal protein S6 and translation initiation factor 4E-binding protein 1, increased expression of eukaryotic elongation factor 2 kinase and decreased expression of programmed cell death protein 4 were associated with poor prognosis in hormone receptor-positive breast cancer.
“Gene expression involves translation of messenger RNAs into protein. The rate of translation is under critical control at many levels; however, recently, several abnormalities in translation have been described in cancer,” said Meric-Bernstam. “We used a functional proteomics approach to quantify the expression and phosphorylation of several factors associated with translation. Several of these proteins have been suggested to play a role in tumor aggressiveness.”
The markers identified are regulated by the PI3K/mTOR signaling pathway, a key oncogenic pathway activated in breast cancer and other cancers, according to Meric-Bernstam. Novel inhibitors of the pathway are being investigated in clinical trials.
“There are recent phase III clinical trial data suggesting that inhibiting mTOR signaling with everolimus, an mTOR inhibitor, in addition to endocrine therapy with aromatase inhibitors improves progression-free survival in hormone receptor-positive breast cancer,” Meric-Bernstam said. “Activation of the pathway conferring poor prognosis provides rationale as to why pathway inhibitors improve outcome.”
The study was funded by an AACR–Stand Up To Cancer Dream Team Award, Susan G. Komen for the Cure, the Society of Surgical Oncology Clinical Investigator Award and the National Institutes of Health Cancer Center Grant.
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About the AACR
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR’s membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.
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