Navigation Links
Leukemia drug reverses tamoxifen-resistance in breast cancer cells
Date:8/1/2011

PHILADELPHIATaking a leukemia chemotherapy drug may help breast cancer patients who don't respond to tamoxifen overcome resistance to the widely-used drug, new research from the Kimmel Cancer Center at Jefferson suggests.

Interestingly, researchers found that taxoxifen combined with dasatinib, a protein-tyrosine kinase inhibitor, reverses the chemo-resistance caused by cancer-associated fibroblasts in the surrounding tissue by normalizing glucose intake and reducing mitochondrial oxidative stress, the process that fuels the cancer cells.

Previous animal studies have confirmed that combining tyrosine kinase inhibitors with anti-estrogen therapies, like tamoxifen, can prevent drug resistance, but none have suggested that the target of the inhibitors is the cancer-associated fibroblasts.

The researchers report their findings in the August 1 issue of Cell Cycle.

About 70 percent of women diagnosed with breast cancer will have estrogen receptor positive (ER(+)) disease, which indicates that the tumor may respond to tamoxifen. However, a large percentage of these tumorsup to 35 percenthave little to no response to the drug or eventually develop resistance to it.

In this study, researchers sought to better understand drug resistance by looking at the metabolic basis in an ER (+) cell line and cancer-associated fibroblasts. The researchers have previously established a relationship between the two, where cancer cells induce aerobic glycolysis by secreting hydrogen peroxide in adjacent fibroblasts via oxidative stress. In turn, these fibroblasts provide nutrients to the cancer cells to proliferate, a process that ultimately makes tumors grow.

Here, they investigated and then demonstrated that this interaction was also the basis of tamoxifen resistance.

In a sense, the drug combination had an "antioxidant effect" in these types of cancer cells, according to Michael P. Lisanti, M.D., Ph.D., Professor and Chair of Stem Cell Biology and Regenerative Medicine at Jefferson Medical College of Thomas Jefferson University and a member of the Kimmel Cancer Center.

"The fibroblasts are what make ER (+) cancer cells resistant to the tamoxifen," said Dr. Lisanti. "But the tamoxifen plus dasatinib maintained both fibroblasts and cancer cells in a 'glycolytic state,' with minimal oxidative stress and more cell death, most likely because of an absence of metabolic coupling. The supply between the two was cut."

"This suggests resistance to chemotherapeutic agents is a metabolic and stromal phenomenal," he added.

Researchers showed that ER (+) cancer cells alone responded to tamoxifen but when co-cultured with human fibroblasts had little to no effect. Similarly, dasatinib, a chemotherapy drug used to treat leukemia patients who can no longer benefit from other medications, had no effect on fibroblasts alone or cancer cells. Together, however, the drugs prevented the cancer cells co-cultured with the fibroblasts from using high-energy nutrients from the fibroblasts.

This combination resulted in nearly 80 percent cell death, the team reporteda two to three fold increase when compared with tamoxifen alone.

"The drugs have no effect when they are used aloneit's in unison when they effectively kill the cancer cells in the presence of fibroblasts," said Dr. Lisanti. "This opens up the door for possible new treatment strategies. This 'synthetic lethality' may help patients overcome resistance in the clinic."


'/>"/>

Contact: Steve Graff
stephen.graff@jefferson.edu
215-512-1783
Thomas Jefferson University
Source:Eurekalert  

Related medicine news :

1. Bone marrow transplant survival more than doubles for young high-risk leukemia patients
2. Half-matched transplants widen pool of donors for leukemia and lymphoma
3. Toward a more efficient therapy for a specific form of leukemia
4. Multitasking meds: Scientists discover how drug for leukemia, psoriasis, may tackle vascular disease
5. Antibody-guided drug works against acute lymphoblastic leukemia
6. Ex-Dallas Maverick survives rare form of leukemia thanks to experimental drug treatment
7. UCSF team discovers key to fighting drug-resistant leukemia
8. Most Leukemia Patients Recover From Chemo Brain After Transplant: Study
9. Agent selectively targets malignant B cells in chronic leukemia, study shows
10. Possible new approach to treating deadly leukemia in babies
11. New drug shows potential for treatment-resistant leukemia
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Leukemia drug reverses tamoxifen-resistance in breast cancer cells
(Date:6/27/2016)... , ... June 27, 2016 ... ... the patient payment industry today announced its strategic partnership with Connance, a ... workflows. , The two companies’ proven, proprietary technology combine to provide health ...
(Date:6/26/2016)... ... 2016 , ... Quality metrics are proliferating in cancer care, and are derived ... eye of the beholder, according to experts who offered insights and commentary in the ... Care. For the full issue, click here . , For the American Society ...
(Date:6/26/2016)... ... ... PawPaws brand pet supplements owned by Whole Health Supply is ... of felines. The formula is all-natural and is made from Chinese herbs that have ... Kidney Support Supplement Soft Chews are Astragalus Root Extract and Rehmannia Root Extract ...
(Date:6/25/2016)... ... 2016 , ... Experts from the American Institutes for Research ... June 26-28, 2016, at the Hynes Convention Center in Boston. , AIR experts ... planning, healthcare costs and patient and family engagement. , AIR researchers will be ...
(Date:6/25/2016)... Aliso Viejo, California (PRWEB) , ... June 25, 2016 , ... ... preset to fit their specific project," said Christina Austin - CEO of Pixel Film ... all fully customizable and all within Final Cut Pro X . Simply select ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016 VolitionRx ... of Dr. Edward Futcher to the ... effective June 23, 2016.Dr. Futcher was also appointed ... Governance Committees.  As a non-executive member of the ... and strategic counsel to VolitionRx in connection with ...
(Date:6/23/2016)... June 23, 2016 Research and Markets ... Market - Forecast to 2022" report to their offering. ... method for the patients with kidney failure, it replaces the ... from the patient,s blood and thus the treatment helps to ... chloride in balance. Increasing number of ESRD ...
(Date:6/23/2016)... , June 23, 2016  In a startling report released today, ... their residents by lacking a comprehensive, proven plan to eliminate prescription ... definitive ranking of how states are tackling the worst drug crisis ... four states – Kentucky , New ... Vermont . Of the 28 failing states, three – ...
Breaking Medicine Technology: