Among the best approaches for reducing the burden of cancer are methods for early diagnosis and monitoring, based on measurement of biomarkers in biological fluids. These biomarkers may facilitate early detection and administration of definitive treatment. The kallikrein gene family has contributed the best cancer marker currently available, prostate-specific antigen. A new kallikrein-like gene, KLK-L2 has been recently (1999) discovered in the author's laboratory. This biomarker exhibits significant similarities with PSA and other kallikreins and it is a secreted protein. In this grant application, it is hypothesized that the newly identified gene KLK-L2 may encode for a potential biomarker protein whose concentration in blood may be altered in the presence of breast cancer. The major aim of this application is to develop the new kallikrein into a potential tumor marker suitable for diagnosis and monitoring of breast cancer. We now know the complete genomic and cDNA sequence of the newly identified kallikrein gene. We will develop recombinant protein, monoclonal antibodies and highly sensitive immunological assays which will be suitable for measurement of the candidate biomarker in biological fluids. In the next step, preliminary clinical studies will be conducted to examine if the newly developed biomarker has any value, either alone or in combination with already known biomarkers, for breast cancer diagnosis, monitoring/prognosis and selection of therapy. Characteristics and similarities of the newly identified gene with already successful cancer biomarkers and its restricted expression to the mammary gland suggest that the newly identified gene holds significant potential for becoming a clinically useful breast cancer marker.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA087615-02
Application #
6378053
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
2000-09-30
Project End
2002-09-29
Budget Start
2001-09-30
Budget End
2002-09-29
Support Year
2
Fiscal Year
2001
Total Cost
$75,000
Indirect Cost
Name
MT Sinai Hosp-Samuel Lunenfeld Research Institute
Department
Type
DUNS #
208808949
City
Toronto
State
ON
Country
Canada
Zip Code
M5 3-L9
Yousef, George M; Polymeris, Mary-Ellen; Grass, Linda et al. (2003) Human kallikrein 5: a potential novel serum biomarker for breast and ovarian cancer. Cancer Res 63:3958-65
Yousef, George M; Scorilas, Andreas; Kyriakopoulou, Lianna G et al. (2002) Human kallikrein gene 5 (KLK5) expression by quantitative PCR: an independent indicator of poor prognosis in breast cancer. Clin Chem 48:1241-50