Over one million women worldwide are diagnosed with breast cancer each year. Roughly 20% of all breast cancers overexpress the human epidennal growth receptor 2 (HER2-positive subtype). HER2-targeted therapies, including Herceptin and lapatinib, account for 55% of the breast cancer therapy market in 2011 (or $5 billion annually). Response to HER2-targeted therapies typically average about one year due to developed resistance. This represents an area of unmet clinical need. HER2 over-expression has been clearly linked to aggressive and abnonnal tumor growth, rapid metastases, and drug resistance in this cancer subtype. siRNA for knocking down HER2 offers a new treatment modality to overcome drug resistance. We are developing a novel nanoparticle platform for therapeutic siRNA delivery. Novelty lies in the hybrid polymeric-inorganic nanoparticles that take full advantage of both classes of materials to overcome siRNA delivery barriers (e.g., poor bioavailability, poor cellular uptake, and off-target effects) and enable large-scale manufacturing of the nanocontruct. This Phase I portion will optimize the nanoparticle platforms to achieve >70% knockdown ofHER2 in three HER2-positive breast cancer cell lines, leading to programmed death of the cancer cells, while having no adverse effect on HER2-negative cells or nonnal cells. The most optimized nanoparticle platform will undergo further in vivo evaluation in Phase II SBIR project.

Agency
National Institute of Health (NIH)
Type
Small Business Innovation Research – Phase I (N43)
Project #
261201300078C-0-0-1
Application #
8762808
Study Section
Project Start
2013-09-20
Project End
2014-06-19
Budget Start
Budget End
Support Year
Fiscal Year
2013
Total Cost
$200,000
Indirect Cost
Name
Pdx Pharmaceuticals, LLC
Department
Type
DUNS #
025852616
City
Lake Oswego
State
OR
Country
United States
Zip Code
97035