In the pharmacogenomic study of NCI60 we have developed strategies to analyze pathway stability by comparing pathway gene expression coherence levels in tumor tissues to their normal counterparts. Changes occurring in cancer as reflected by variations in pathway coherence are considered to be indicative of pathway instability and possibly genetic instability. We have identified pathways that show a significant change in their coherence level in tumor tissues in general, as well as specific changes in certain tumor types. These pathways may represent good targets for developing novel anti-cancer therapies.

Significantly more pathways are found to lose their coherence in tumor tissues. Signal transduction represents the most unstable pathway category, whose coherence in gene regulation is largely lost in tumor tissues. In contrast, pathways responsible for vital cellular processes are mostly able to maintain their gene expression coherence in tumor tissues and are among the most stable. The combination of homeostatic control over critical pathways to ensure survival, and altered regulation of signaling to allow excessive proliferation, forms the foundation for the selective growth advantage of cancer cells over normal cells.

The instability of metabolic and cell cycle regulating pathways appear to be the most tissue-specific. The function of these pathways and their unstable tissue type may provide important clues for finding the molecular mechanisms underlying specific cancer types. We have examined the particular pathways that contain known cancer genes and compared their behavior with other pathways. Cancer pathways are found more likely to lose their coherence and thus show a greater level of instability than an average pathway. Finally, we have proposed strategies to target these changes, that is, to find new agents that can specifically target the unstable pathways that may be relevant in cancer.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

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