USA and WHO global cancer statistics indicate little improvement in incidence and mortality rates from breast cancer and gastric cancer. Genomics data from the first completed breast cancer genome sequence using next-generation sequencing technology reveal a huge number of mutations in both protein-coding (exome) and non-protein areas of this genome. These mutations include “point mutations (SNPs, insertions, deletions), genomic rearrangements and copy-number variants (CNVs). These findings together with the first results from the pilot phase of the 1000 Genome Project and systematic genomic studies reveal now that solid cancers including breast and gastric cancer are much more complex and heterogeneous than we anticipated. If we don't change current convention molecular single-gene(s) research, the estimates by the WHO for the year 2020 for a 50% increase in cancer incidence rates making cancer the top health problem worldwide will be become a reality.
The large number and variability of mutations in each individual cancer patient limits the expectations for the development of biomarkers and drugs effective in the prevention or treatment setting. Alternatively, tumors scanning for characterizing signaling downstream pathways that are deregulated by these mutations appears more realistic goal given that a few only, about maximum one dozen of these pathways are deregulated.
In this perspective article, the latest advances are described that suggest that biological systems interactions and molecular networks including signaling pathways networks in each individual cancer cell and intratumoral cell-cell interactions drive tumorigenesis and metastasis rather than a simple accumulation of mutations.
Research efforts with focus on how to predict the inference of dynamic nonlinear complex systems such as biological systems using innovative methods with integrated systems biology approaches and network modeling open the door towards a next-generation of robust biomarkers and active therapeutics against breast and gastric cancer.
(Citation: Gastric & Breast Cancer 2010
Oct ; 9(4): 127-143)
Keywords: breast cancer genome, next-generation sequencing technology, gastric cancer; systems biology; molecular networks; drugs; biomarkers.
This article contains 3 Tables & 2 Figures.