Navigation Links
TGen-US Oncology data guides treatment of metastatic triple-negative breast cancer patients
Date:12/6/2012

PHOENIX, Ariz. Dec. 6, 2012 Genomic sequencing has revealed therapeutic drug targets for difficult-to-treat, metastatic triple-negative breast cancer (TNBC), according to an unprecedented study by the Translational Genomic Research Institute (TGen) and US Oncology Research.

The study is published by the journal Molecular Cancer Therapeutics and is currently available online.

By sequencing, or spelling out, the billions of letters contained in the genomes of 14 tumors from ethnically diverse metastatic TNBC patients, TGen and US Oncology Research investigators found recurring significant mutations and other changes in more than a dozen genes. In addition, the investigators identified mutations previously unseen in metastatic TNBC and took the sequencing data into account in selection of therapeutic protocols specific to each patient's genetic profile.

"This study stands as a one-of-a-kind effort that has already led to potentially beneficial clinical trials, and sets the stage for future investigations," said Dr. John Carpten, Ph.D., TGen's Deputy Director of Basic Science and Director of TGen's Integrated Cancer Genomics Division, and the study's senior author.

The most frequently mutated gene among the tumors (seven of 14) was the TP53 tumor suppressor, and aberrations were observed in additional tumor suppressor genes including CTNNA1, which was detected in two of six African American patients (who typically have more aggressive and treatment-resistant disease). Alterations were also seen in the ERBB4 gene, known to be involved in mammary-gland maturation during pregnancy and lactation, but not previously linked to metastatic TNBC.

The study included an "outlier analysis," which assessed expression patterns for each tumor when compared against the other tumors examined in the study. Specific cancer genes overexpressed among tumors in the study's cohort included: ALK, AR, ARAF, BRAF, FGFR2, GLI1, GLI2, HRAS, HSP90AA1, KRAS, MET, NOTCH2, NOTCH3, and SHH. Significantly underexpressed cancer genes included: BRCA1, BRCA2, CDKN2A, CTNNA1, DKK1, FBXW7, NF1, PTEN, and SFN.

Each tumor was genomically unique, but nine of the 14 contained alterations in one or both of two particular cellular pathways: RAS/RAF/MEK/ERK and PI3K/AKT/MTOR. Targeted therapeutic intervention aimed at these pathways achieved impressive responses in several cases.

"Importantly, the analysis provided insights into the potential unique therapeutic vulnerabilities of each cancer," said Dr. Joyce O'Shaughnessy, M.D., the study's other co-lead author. Dr. O'Shaughnessy is a practicing oncologist with Texas Oncology an affiliate of The US Oncology Network and is the Celebrating Women Chair of Breast Cancer Research at Baylor Charles A. Sammons Cancer Center.

Metastatic TNBC is a highly aggressive form of breast cancer that disproportionately affects African-Americans. It is called triple-negative because tumors do not express the estrogen receptor, progesterone receptor or HER-2, the biomarkers successfully targeted in most breast cancers.

Metastatic TNBC also has a poor prognosis once the cancer has spread to other organs, with a median survival rate among metastatic patients of only one year. While TNBC accounts for only about 15 percent of all breast cancers, its more aggressive biology makes it responsible for nearly one in four deaths related to this disease.

"The nature of this disease cries out for innovative research techniques such as whole genome sequencing coupled with new tools for data analysis," said Dr. David Craig, Ph.D., TGen's Deputy Director of Bioinformatics, and one of the study's co-lead authors.

"We are aware that these results are preliminary and based on a small series of patients," said Carpten. "However, our study will pave the way for new clinical trials and novel hypotheses for future testing in a very difficult to treat cancer."

Whole-genome sequencing of tumors and normal tissue was performed on Life Technologies Corporation's Applied Biosystems SOLiD 4.0 platform, and results were validated in a CLIA-certified laboratory.


'/>"/>

Contact: Steve Yozwiak
syozwiak@tgen.org
602-343-8704
The Translational Genomics Research Institute
Source:Eurekalert

Related biology news :

1. ESMO 2012 Congress: A path for medical oncology innovations
2. Nanotechnology drug delivery shows promise for treatment of pediatric cancer
3. ALS TDI and Gladstone Institutes collaborate to discover potential ALS treatments
4. Protein injection points to muscular dystrophy treatment
5. Possible new treatment for Ewing sarcoma
6. Combination of two pharmaceuticals proves effective in the treatment of multiple sclerosis
7. Notre Dame research could improve sustainability and cost effectiveness of wastewater treatment
8. Bringing measuring accuracy to radical treatment
9. Superbug MRSA identified in US wastewater treatment plants
10. Scientists unravel resistance to breast cancer treatment
11. FDA Grants Meridian Laboratories Pre-Ind Meeting for Captisol-Enabled Docetaxel in the Treatment of Cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/1/2016)... , February 1, 2016 ... advancements to drive global touchfree intuitive gesture control market ... --> Rising sales of consumer electronics coupled with ... control market size through 2020 ... electronics coupled with new technological advancements to drive global ...
(Date:1/27/2016)... Ohio , Jan. 27, 2016  Rite Track, ... based in West Chester, Ohio ... award winning service staff, based in Austin, ... capacity and ability to provide modifications, installations and technical ... Dovalina , CEO of PLUS, commented, "PLUS has provided ...
(Date:1/22/2016)... http://www.researchandmarkets.com/research/p74whf/global_biometrics ) ... "Global Biometrics Market in Retail Sector 2016-2020" ... --> http://www.researchandmarkets.com/research/p74whf/global_biometrics ) has announced the ... in Retail Sector 2016-2020" report to ... and Markets ( http://www.researchandmarkets.com/research/p74whf/global_biometrics ) has announced ...
Breaking Biology News(10 mins):
(Date:2/6/2016)... ... February 06, 2016 , ... Contact:, Abby Mitchell, ... Excellence in Education Sponsors Teacher Training Program , Bite of Science Dinner Event ... Center for Excellence in Education (CEE) will sponsor a Bite of Science professional ...
(Date:2/5/2016)... DIEGO , Feb. 5, 2016 On ... region,s trusted information source for community, health and disaster ... Diego) will integrate to enhance care coordination and ... to the services they need and to better connect ... improve care.   San Diego ...
(Date:2/4/2016)... ... February 04, 2016 , ... ... and compliance training, today announced an interactive FDA compliance training course, ... RAPS (Regulatory Affairs Professional Society) accredited interactive course on Morf Playbook—now conveniently available ...
(Date:2/4/2016)... ... February 04, 2016 , ... ... and triple quad LC-MS, host live demos and poster sessions, and present on ... exhibition. The conference takes place March 6 to 10 at the Georgia World ...
Breaking Biology Technology: