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Impact of Biomarkers on Management of Cancer
Biomarkers are playing an important role in the diagnosis as well as management of
cancer. Some examples are given here.
HER-2/neu Oncogene as a Biomarker for Cancer
HER-2/neu oncogene, also referred to as c-erbB-2, encodes a protein with a molec-
ular weight of 185,000 Da and is structurally related to the human epithelial growth
factor receptor. The full length p185 HER-2/neu protein is composed of a cytoplas-
mic domain with tyrosine kinase activity, a transmembrane domain and an extracel-
lular domain (ECD) that is shed from the surface of breast cancer cells. Numerous
studies have shown that the shed ECD of HER-2/neu is a glycoprotein with a molec-
ular weight between 97 and 115 kDa and designated p105. The ECD can be accu-
rately quantifi ed in serum with an ELISA that uses MAbs directed to the external
epitopes of the HER-2/neu protein. Many publications show that the ECD is shed
into the blood of normal individuals and can be elevated in women with metastatic
breast cancer. Many of these serum HER-2/neu studies have confi rmed the substan-
tial data from tissue studies that HER-2/neu is a biomarker of poor prognosis,
shorter overall survival and biological aggressiveness. Scientifi c studies suggest that
quantitation of the ECD may have several important clinical applications such as
monitoring breast cancer patients with metastatic disease.
Various reports have shown that 30–50 % of women with positive HER-2/neu
tumors at primary diagnosis develop elevated levels of serum HER-2/neu with pro-
gression to metastatic breast cancer. These studies have also illustrated that moni-
toring serum ECD levels post-surgery correlated with clinical course of disease and
that serum HER-2/neu levels were observed to increase with disease progression or
to decrease with response to therapy. Several reports also show that elevated levels
of serum HER-2/neu can occur in women with metastatic breast cancer that had
primary breast tumors that were negative for HER-2/neu expression by immunohis-
tochemistry. According to many IHC and serum studies, the HER-2/neu protein is
overexpressed in many tumors of epithelial origin including lung, prostate, pancre-
atic, colon, stomach, ovarian, and hepatocellular cancer.
L-Asparaginase Treatment of Cancer Guided by a Biomarker
L-asparaginase (L-ASP), a bacterial enzyme used to treat acute lymphoblastic leu-
kemia, selectively starves cells that cannot synthesize suffi cient asparagine for their
own needs Studies show that cancer cells that contain less asparagine synthetase
(ASNS) are more susceptible to L-ASP. The response to L-ASP therapy is often
better when the expression of ASNS is limited. A new method has been described
10 Personalized Therapy of Cancer