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Akt-Ser473 Phosphorylation as a Marker for Predicting Taxane Chemotherapy Outcome

Posted Jun 06 2010 5:00pm

Description of Invention:
Over the past decades, taxanes such as paclitaxel and docetaxel have emerged as effective chemotherapy agents for breast cancer and other malignancies. Taxanes are effective in many patients, however, not all patients benefit from this type of chemotherapy. A significant need remains for a means of predicting clinical outcome from taxane-based chemotherapy.

Akt, a serine/threonine kinase that can block apoptosis, has been implicated in the regulation of microtubule dynamics and organization. Akt phosphorylation and its transducing downstream events play a central role in cell survival and cell cycle progression at the G2/M transition. Paclitaxel or docetaxel inhibits Akt-Ser473 phosphorylation (pAkt) and induces mitotic arrest. Therefore, taxanes may cause more damage to tumor cells that are dependent on pAkt for survival and cell cycle progression, significantly impacting treatment outcome.

Researchers at the National Cancer Institute, NIH, have identified pAkt as having predictive significance for paclitaxel chemotherapy outcome in patients with early stage breast cancer. The researchers have developed an immunohistochemistry method for determining pAkt status with appropriate controls for assay performance and cutoff for pAkt positivity. They also discovered methods of correlating pAkt expression with clinical outcome (disease-free survival and overall survival). pAkt is a novel predictive marker of taxane chemotherapy, and can be applied to indicate which patients should receive taxane-based chemotherapy.

Applications:
A kit for identifying pAkt-positive tumors in surgical tumor specimens or tumor biopsies prior to treatment (adjuvant, neoadjuvant therapy or therapy for metastatic disease); and methods for predicting clinical outcome from taxane chemotherapy.

Advantages:
pAkt is a useful clinical predictive marker to determine which patients should or should not receive taxane-based chemotherapy for cancer. Determining pAkt status would allow patients with pAkt-positive tumors to elect taxane therapy for whom are likely to benefit, and allow patients with pAkt-negative tumors for whom are unlikely to benefit to be spared from taxane therapy as well as toxicity, and earlier use of other therapies that could be more effective. The application of this invention may potentially reduce the cost of cancer care.

Inventors:
Sherry X Yang (NCI)


Patent Status:
HHS, Reference No. E-191-2009/0
PCT, Application No. PCT/US2010/035816 filed 21 May 2010


Relevant Publication:
  1. Yang, SX, Costantino JP, Mamounas EP, Nguyen D, Jeong J-H, Wolmark N, Kim C, Kidwell K, Paik S, Swain SM. Correlation of levels of Akt phosphorylation at Ser473 with benefit from paclitaxel chemotherapy in NSABP B-28 patients with node-positive breast cancer. J Clin Oncol. 2009 (May 20 Supplement);27(15S):537.
  2. Yang SX, Costantino JP, Mamounas EP, Nguyen D, Jeong J-H, Wolmark N, Kim C, Kidwell K, Paik S, Swain SM. Akt phosphorylation at Ser473 predicts benefit to paclitaxel chemotherapy in node-positive breast cancer. J Clin Oncol. 2010, In Press.


Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the pAkt assay for use in a clinical setting. The National Cancer Institute would be particularly interested in discussing collaborations to provide additional clinical validation of pAkt as a primary biomarker. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.


Portfolios:
Cancer
Cancer - Diagnostics



For Additional Information Please Contact:
Patrick McCue Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: McCuepat@mail.nih.gov
Phone: 301-496-7057
Fax: 301-402-0220


Ref No: 2084

Updated: 06/2010

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