Navigation Links
Signaling pathway linked to inflammatory breast cancer may drive disease metastasis
Date:11/13/2011

SAN FRANCISCO Amplification of anaplastic lymphoma kinase, which has been reported in other cancers such as non-small cell lung cancers, may be a primary driver of the rapid metastasis that patients with inflammatory breast cancer experience.

If validated, the use of anaplastic lymphoma kinase (ALK) inhibitors may be a new treatment approach for patients with this lethal form of breast cancer.

These data were presented at the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, held Nov. 12-16, 2011.

"A diagnosis of inflammatory breast cancer carries with it a very low five-year survival rate of about 40 percent, clearly indicating the critical need for an understanding of the molecular basis of the disease," said Fredika M. Robertson, Ph.D., professor in the department of experimental therapeutics at The University of Texas M.D. Anderson Cancer Center and a member of the Morgan Welch Inflammatory Breast Cancer Research Program. "However, there are few molecules that have been identified that are matched with available targeted therapies of clinical benefit in patients with inflammatory breast cancer."

Robertson and colleagues used patient-derived tumors, tumor cell lines and animal models to evaluate protein-signaling pathways and genetic abnormalities with the goal of identifying molecules that may be associated with the increased metastases of inflammatory breast cancer. They discovered ALK amplification in 13 of 15 tumor samples taken from patients with this lethal variant of breast cancer. They then validated the presence of this abnormality in tumor cell lines and newly developed xenograft models.

Gene amplification of ALK is only found in about 2 percent of the overall breast cancer population, according to Robertson. However, results from this analysis indicate that in inflammatory breast cancer, it could be occurring in up to 86 percent of patients.

"The observation that ALK is amplified may be comparable to the observation of HER2 oncogene amplification in some cases of breast cancer, which revolutionized how the disease was treated," Robertson said. "Our observation that ALK is amplified in inflammatory breast cancer suggests that ALK may serve as a good target for treatment."

To test this, the researchers evaluated the effects of a drug that inhibits ALK using tumor cells isolated from patients with metastatic inflammatory breast cancer and in two animal models that recapitulate the disease. Results indicated that the use of this drug resulted in tumor cell death.

"Patients with inflammatory breast cancer are now being evaluated for ALK genetic abnormalities, and if found and eligible, may be enrolled in a phase 1, dose-escalation clinical trial of a small-molecule ALK/cMet inhibitor," Robertson said. She added that Massimo Cristofanilli, M.D., chair of medical oncology at Fox Chase Cancer Center in Philadelphia has implemented this trial at the center's Inflammatory Breast Cancer Clinic.

Moving forward, Robertson emphasized the importance of collaborating with a research team with expertise in using both proteomic and genomic approaches to define molecular biology of tumors, to identify therapeutic targets and, once validated, to rapidly translate these findings to the clinic.

"Our results demonstrate that, had we only been using genomic platforms, the likelihood of identifying ALK as a therapeutic target would have been significantly diminished," she said.


'/>"/>

Contact: Jeremy Moore
Jeremy.Moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

Related biology news :

1. New book on calcium signaling from Cold Spring Harbor Laboratory Press
2. Scripps Research scientists pinpoint shape-shifting mechanism critical to protein signaling
3. Molecular chaperones traffic signaling proteins between cells in plant stem-cell maintenance pathway
4. NYU Langone researchers identify a signaling pathway as possible target for cancer treatment
5. Animal model sheds light on rare genetic disorder, signaling pathway
6. Signaling pathway is executive software of airway stem cells
7. Study reveals important aspects of signaling across cell membranes in plants
8. Experimental drug inhibits cell signaling pathway and slows ovarian cancer growth
9. A new signaling pathway of the immune system is elucidated
10. Signaling path in brain may prevent that Im full message, UT Southwestern scientists discover
11. Nailing down a crucial plant signaling system
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/23/2017)... and ITHACA, N.Y. , ... and Cornell University, a leader in dairy research, today ... bioinformatics designed to help reduce the chances that the ... the onset of this dairy project, Cornell University has ... for Sequencing the Food Supply Chain, a food safety ...
(Date:5/6/2017)... , May 5, 2017 ... just announced a new breakthrough in biometric authentication ... exploits quantum mechanical properties to perform biometric authentication. These ... smart semiconductor material created by Ram Group and ... finance, entertainment, transportation, supply chains and security. Ram ...
(Date:4/13/2017)... MONICA, Calif. , April 13, 2017 ... New York will feature emerging and evolving ... Summits. Both Innovation Summits will run alongside the expo ... of speaker sessions, panels and demonstrations focused on trending ... coast,s largest advanced design and manufacturing event will take ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... 11, 2017 , ... Proscia Inc ., a data ... titled, “Pathology is going digital. Is your lab ready?” with Dr. Nicolas Cacciabeve, ... and how Proscia improves lab economics and realizes an increase in diagnostic confidence.* ...
(Date:10/11/2017)... ... 11, 2017 , ... A new study published in Fertility ... fresh in vitro fertilization (IVF) transfer cycles. The multi-center matched cohort ... After comparing the results from the fresh and frozen transfer cohorts, the authors ...
(Date:10/10/2017)... ... October 10, 2017 , ... For the ... won a US2020 STEM Mentoring Award. Representatives of the FirstHand program travelled to ... Experience from US2020. , US2020’s mission is to change the trajectory of STEM ...
(Date:10/10/2017)... ... October 10, 2017 , ... ... process optimization firm for the life sciences and healthcare industries, announces a presentation ... San Francisco. , The presentation, “Automating GxP Validation for Agile Cloud Platforms,” will ...
Breaking Biology Technology: