Navigation Links
Treatment targeting PI3K may delay resistance to anti-HER2 therapy in breast cancer patients

PHILADELPHIA Patients with HER2-positive breast cancer being treated with anti-HER2 therapy may be able to prevent or delay resistance to the therapy with the addition of a phosphatidylinositol-3 kinase inhibitor to their treatment regimens.

The data, published in Cancer Research, a journal of the American Association for Cancer Research, indicated that failure of the anti-HER2 antibody trastuzumab to block HER2 from activating the phosphatidylinositol-3 kinase (PI3K) signaling pathway can lead to resistance to treatment. Therefore, dual simultaneous inhibition of both HER2 and PI3K may prolong the use of anti-HER2 therapies in women with breast cancer.

"HER2 breast cancer is a subtype of breast cancer for which we have an increasing number of effective treatments, including trastuzumab, an antibody that targets HER2," said Carlos L. Arteaga, M.D., director of the Breast Cancer Program at Vanderbilt-Ingram Cancer Center in Nashville, Tenn. "Unfortunately, many breast cancer tumors learn how to resist this therapy."

Arteaga and colleagues explored the possibility that aberrant signaling through the PI3K pathway was a mechanism of resistance to trastuzumab. They used breast cancer models of trastuzumab resistance with different modes of aberrant PI3K pathway activation, and treated the cells with a PI3K inhibitor with or without trastuzumab.

Inhibiting PI3K reduced cancer cells' ability to proliferate and induced the death of trastuzumab-resistant cells. In addition, combining PI3K inhibitors with trastuzumab resulted in superior anti-tumor effects against trastuzumab-resistant, HER2-positive cells in xenografts compared with the PI3K inhibitor alone.

The investigators also conducted analyses to determine how the drug combination decreased resistance to trastuzumab.

"We found that the trastuzumab-resistant cells in which the PI3K pathway was activated had high levels of an anti-death protein called survivin," Arteaga said. "This implied that if we could get levels of survivin to decrease, these cells would become sensitive to treatment."

They also measured pretreatment levels of survivin in HER2-positive breast cancer tumors and found that higher pretreatment levels of the protein correlated with a poor response to therapy.

"This suggests that we could measure levels of survivin in tumors, and if they are high or do not decrease with treatment, we could predict that the tumor is resistant to anti-HER2 therapy and try to find alternative treatments," Arteaga said.

Arteaga and colleagues plan to continue testing PI3K inhibitors, which are already in early clinical development, in combination with other HER2 drugs in breast cancer. They also plan to measure survivin levels in HER2-overexpressing breast cancer tumors to determine if levels can predict tumors that will benefit from combination treatment.

Contact: Jeremy Moore
American Association for Cancer Research

Related medicine news :

1. Scientist awarded $1 million grant to develop tools for hepatitis C treatment discovery
2. Clinical insight improves treatment with new lung cancer drug
3. Rapid Asthma Treatment in ER May Prevent Admission
4. Novel compound demonstrates anti-leukemic effect in zebrafish, shows promise for human treatment
5. Breast cancer patients suffer treatment-related side effects long after completing care
6. Mayo Clinic offers newly approved treatment for acid reflux disease
7. Mobile Stroke Units Might Trim Time to Treatment
8. Breast Cancer Treatment Side Effects May Last for Years
9. Mouse Study Hints at New Path for Diabetes Treatment
10. Symptomatic behaviour in childhood strongly predicts psychiatric treatment as a young adult
11. Exercise improves quality of life during breast cancer treatment
Post Your Comments:
(Date:11/25/2015)... ... 2015 , ... The McHenry County law firm of Botto Gilbert Lancaster, ... Francisco J. Botto and Alex C. Wimmer. Attorneys Botto and Wimmer represented the claimant ... (2d) 130884WC. , According to court documents, Adcock testified that on May 10, 2010 ...
(Date:11/25/2015)... ... ... SCOTTSDALE, AZ) - Today, Dr. Todd C. Hobgood ... non-surgical treatments, announced the expansion of his private practice capabilities with the grand ... trained and nationally recognized for his natural approach, Dr. Todd Hobgood serves the ...
(Date:11/25/2015)... ... November 25, 2015 , ... In an ongoing Clinical Study conducted ... in Chicago, IL, UV Angel is evaluating the efficacy of its product and its ... units (totaling 30 beds) from May 2014 through October 2015 at a 360-bed, acute-care, ...
(Date:11/25/2015)... ... November 25, 2015 , ... ... scholarships for people struggling with eating disorders as a result of the $20,000 ... annual event, held at Fox Run Golf Club in Eureka, will help individuals ...
(Date:11/25/2015)... Davie, Florida (PRWEB) , ... November 25, 2015 ... ... PharmaTech LLC has announced that it has undertaken significant expansion of its current ... Florida. The investment is part of PharmaTech’s strategy to increase its manufacturing capacity ...
Breaking Medicine News(10 mins):
(Date:11/24/2015)... BOULDER, Colo. , Nov. 24, 2015 /PRNewswire/ ... announced that its Chief Executive Officer, Ron ... Annual Healthcare Conference in New York.  The public ... a webcast on the Array BioPharma website.Event:Piper Jaffray ... OfficerDate:  , Wednesday, December 2, 2015Time:1:30 p.m. Eastern ...
(Date:11/24/2015)... New York , 24. November 2015 ... des Avery Breathing Pacemaker Systems, ist erfreut, ... als Clinical Consultant bekannt geben zu können. ...   --> Foto ... Stockholm (Schweden). Von 1984-1986 war ...
(Date:11/24/2015)... 24, 2015 Avery Biomedical Devices (ABD), manufacturer ... announce the appointment of Anders Jonzon , MD; ... Dr. Jonzon is a Physiologist ... Hospital, Uppsala University, Uppsala and Children,s Hospital, Karolinska, ... a fellow at the Cardiovascular Institute (UCSF). His research ...
Breaking Medicine Technology: