6 A Practical Guide to Cancer Systems Biology
of this book, we will demonstrate how to use homology modeling and docking
simulation for drug discovery.
3.2. Molecular regulation
3.2.1. Gene expression profiles for molecular regulation
Comparing the gene expression profiles after drug treatment or not, we are
able to study the molecular mechanism of the drug in cancer cells. Combining
time-series gene expression measurements and network construction, and
further validation by real-time quantitative polymerase chain reaction (Q-
PCR), scientists can reconstruct novel drug-response networks which provide
molecular explanations of the drugs. Using this approach, we reconstructed
an apoptosis-related gene network which is induced by a novel synthetic
compound cRGD in human breast cancer cells.^16 This study may create an
impact on breast cancer therapy.
This strategy of using gene expression and network studies can not only
be applied to synthetic drugs but also to natural products.Ganoderma
lucidum has been used in traditional Chinese medicine with antitumor
and immuno-modulatory effects. From microarray gene expression studies
and network construction, we found novel molecular mechanism in natural
products. As shown in the papers, we extracted natural products from
Ganoderma lucidumand found polysaccharides designated as F3 can induce
macrophage-like differentiation via receptor oligomerization, recruitment of
specialized adaptor proteins, caspase and p53 activation.17,
The strategy described above can also be used to study molecular
regulation. In these studies, we used proteomics to discover annexin A
(ANXA4) as a novel biomarker for gastric cancer and further performed
exon array to elucidate its molecular function in gastric cancer cells. We
demonstrated that ANXA4 binds to plasma membrane in a Ca2+-dependent
manner and induces downstream signaling transduction that promote cell
growth.^19
3.2.2. Proteomes for molecular regulation studies
Proteomics can speed up the process of discovering cancer biomarkers
and drug targets as well as the study of molecular regulations of drugs
or non-coding RNAs. The global changes of protein expression in normal
and disease situations can be visualized and compared with 2-DE and
further identified by MS analysis.8,14,15ATP synthase was highly expressed
in breast and lung cancer patients and reported as a potential drug