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:3/28/2017)... , March 28, 2017 The ... Hardware (Camera, Monitors, Servers, Storage Devices), Software (Video Analytics, ... Region - Global Forecast to 2022", published by MarketsandMarkets, ... 2016 and is projected to reach USD 75.64 Billion ... and 2022. The base year considered for the study ...
(Date:3/24/2017)... 24, 2017 The Controller General of Immigration from ... Abdulla Algeen have received the prestigious international IAIR Award for the ... Continue Reading ... ... Controller Abdulla Algeen (small picture on the right) have received the IAIR ...
(Date:3/23/2017)... The report "Gesture Recognition and Touchless Sensing Market by Technology (Touch-based ... to 2022", published by MarketsandMarkets, the market is expected to be worth USD ... 2022. Continue Reading ... ... ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... and LAGUNA HILLS, Calif. , Oct. ... Cancer Research, London (ICR) and University ... SKY92, SkylineDx,s prognostic tool to risk-stratify patients with multiple myeloma ... MUK nine . The University of Leeds ... partly funded by Myeloma UK, and ICR will perform the ...
(Date:10/10/2017)... ... 2017 , ... San Diego-based team building and cooking events company, Lajollacooks4u, has ... The bold new look is part of a transformation to increase awareness, appeal to ... period. , It will also expand its service offering from its signature gourmet cooking ...
(Date:10/10/2017)... 10, 2017 International research firm Parks Associates announced ... at the TMA 2017 Annual Meeting , October 11 in ... residential home security market and how smart safety and security products impact ... Parks Associates: Smart Home ... "The residential security market has ...
(Date:10/9/2017)... DIEGO , Oct. 9, 2017  BioTech ... biological mechanism by which its ProCell stem cell ... critical limb ischemia.  The Company, demonstrated that treatment ... amount of limbs saved as compared to standard ... the molecule HGF resulted in reduction of therapeutic ...
Breaking Biology Technology: