In cancer and other diseases such as Alzheimer's disease and inflammatory diseases, the signal transduction pathways within cells are often observed to be hyperactive and dominant or hypoactive. For example, defective, hyperactive or dominating signal pathways appear to drive cancer growth, survival, invasion and metastasis (Liotta and Kohn, “The microenvironment of the tumor-host interface,” Nature 411: 375-379, 2001). The hyperactive pathway observations do not necessarily indicate the presence of greater amounts of protein or mRNA, but rather are a consequence of altered activation states of pathway components, and from altered interactions (cross-talk) between pathways that are separated in normal cells, but linked in tumor cells. Recognizing that signaling pathways may be targeted for therapy, pharmaceutical companies are developing specific inhibitors of pathway components such as tyrosine kinases. Unfortunately, efficacious doses of these drugs are often so high that they result in non-specific binding to molecules outside of the targeted pathway, and thus toxicity. Furthermore, diseased cells are often observed to develop resistance to the agents due to shunting around targeted pathway components and/or development of alternative signaling pathways.
USPTO Backgrounds
USPTO Backgrounds