Navigation Links
Treatment targeting PI3K may delay resistance to anti-HER2 therapy in breast cancer patients
Date:1/23/2013

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
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:7/25/2017)... ... July 25, 2017 , ... ... launch of their partnership to provide the Pharmacist eCare Plan to ... in the country with the ability to develop the Pharmacist eCare Plan, a ...
(Date:7/25/2017)... ... July 25, 2017 , ... ... provider in the United States, today announced its partnership with financial technology company, ... , The foundation of the solution lies within Hyosung’s superior ATMs, assisted self-service ...
(Date:7/25/2017)... TX (PRWEB) , ... July 25, 2017 , ... SignatureCare ... emergencies in the Austin, TX area 24 Hours a day. , The ... Austin, TX. , “We’ve been open four months now and things are running ...
(Date:7/24/2017)... , ... July 24, 2017 , ... SignatureCare Emergency ... will be awarded for the fall semester to a deserving student. Get your ... Spring 2017 scholarship was awarded to Mariana Castillo who is a nursing student at ...
(Date:7/24/2017)... ... July 24, 2017 , ... A ... destroyed the construction site and threatened numerous homes and businesses nearby, causing some ... on NBCLosAngeles.com. Los Angeles Area consulting firm Fire Protection Group, Inc. notes ...
Breaking Medicine News(10 mins):
(Date:7/25/2017)... July 25, 2017  Debbie,s Dream Foundation: Curing Stomach Cancer (DDF) is excited ... 25, 2017 at the Bonaventure Resort & Spa in Weston, Florida ... ... President Debbie Zelman, and Luncheon Committee Co-chair Sabrina Kurzman. ... Aura Morales-Guzman, Angela Perez, ...
(Date:7/21/2017)... DUBLIN , July 21, 2017  Endo International ... after completing a comprehensive review of its manufacturing network, ... manufacturing and distribution facilities in Huntsville, Alabama ... to take place over the next 12 to 18 ... been impacted by declining volumes of commoditized products and ...
(Date:7/15/2017)... Enterin Inc., a Philadelphia -based ... today announced the completion of a $12.7 million Series A ... as well as the participation of existing investors. ... the support of New Ventures III and our current investors, ... the potential of our platform technology to transform the course ...
Breaking Medicine Technology: