A&G PHARMACEUTICAL, INC. — Department of Health and Human Services SBIR Phase I: NCI

Description

Significance Despite decreases in the overall number of new breast cancer BC cases reported in the US annually there are still about BC deaths annually from metastatic breast cancer MBC Thus the ability to monitor MBC is important to determine disease status and therapy response While the gold standard imaging is expensive time consuming and slow to detect disease response or progression circulating biomarkers such as CA CA and CEA also used to monitor MBC have limitations due to low specificity and sensitivity Thus providing better safe inexpensive non invasive specific and sensitive tests for new biomarkers to monitor disease is a key component in improving MBC patient care Strategy Measurement of critical biological drivers as biomarkers of the disease will provide a clearer understanding of current disease state and improve proactive clinical management The PI has characterized a proprietary target biomarker GP expressed in BC tissue secreted in BC patients blood and playing a key role in BC tumorigenesis GP IHC and EIA tests to measure GP tumor expression and circulating levels in BC patients were developed and clinically validated Supporting Evidence Pathological studies have established GP tumor expression as a predictive marker for recurrence Clinical studies have shown BC patients with progressive disease have elevated GP serum levels compared to patients with no evidence of disease or healthy individuals Patients with poor outcome had a significantly higher GP serum levels ng ml range ng ml than alive patients ng ml range ng ml p These data indicate that if GP blood levels are maintained below a yet to be established cut off level then a patient can be expected to have a longer survival than patients with elevated GP Hypothesis Measuring serum GP level could provide an ideal approach for monitoring disease status in MBC patients as adjunctive to imaging This hypothesis will be investigated by measuring GP levels in sequential retrospective serum samples collected from MBC patients enrolled in an IRB approved study at UMGCCC and correlate such levels with objective measures of clinical outcome determined using RECIST criteria Specific Aims we will a establish by Kaplan Meier survival graphs a GP threshold value that stratify BC patients for survival and clinical outcomes b determine if changes in GP serum level correlate with changes in RECIST criteria collected at the same time points using receiver operating characteristics curves identify GP cutoff values that effectively stratify patients by their clinical outcome using multivariate analysis and logistic regression evaluate if combining GP and CA results can improve upon and enhance the predictive performance of CA Overall Impact Since GP is a driver of the disease the use of the GP EIA test has the potential to provide real time evaluation of the disease state making GP a better biomarker to monitor MBC than those currently available This will provide clinicians with a new assay to assess disease status to increase predictive values of existing techniques such as imaging Of breast cancer BC related deaths are where BC has spread outside the breast MBC even though at time of primary diagnosis there is often no evidence of tumor spread Thus the ability to detect and monitor MBC is important in the management of BC Provision of safe inexpensive non invasive specific and sensitive tests for monitoring of disease is key in disease management The PI has characterized a biomarker called GP Biological and clinical studies have established the importance of GP in BC aggressiveness and as a predictive marker for recurrence Published studies demonstrated GP is present in BC tissue but not in corresponding normal breast tissue elevated levels of GP in BC tumor tissue are associated with poor outcome and compared to healthy individuals elevated GP blood levels can be found in BC patients with progressive disease Thus using blood tests to detect and quantify GP during treatment could provide an ideal target for monitoring disease progression in BC patients undergoing therapy This SBIR Phase I study will measure GP levels in sequential blood samples collected from MBC patients enrolled in an IRB approved study and correlate such levels with objective measures of clinical outcome This application will explore this relationship and determine the best cutoff level for GP when examining sequential data in comparison to disease status If we can establish a relationship between the GP level in blood and the disease state the information will be useful for disease management of MBC patients