PQ - 18 Are there new technologies to inhibit traditionally "undruggable" target molecules, such as transcription factors, that are required for the oncogenic phenotype? Background: Many tumor cells are known to be dependent on the expression and function of transcription factors or other proteins that are not easily targeted by standard drug development strategies. Typically, these proteins do not have enzymatic activities that can be inhibited by small molecule organic drugs. Nevertheless, cancer cells are often fully dependent on the continued expression and biological activity of these proteins, as shown by RNAi experiments or other functional tests. Many groups have tried to identify small molecule inhibitors that would interfere with the function of these proteins by blocking their interaction with other essential proteins. However, except for rare cases, these approaches have not led to drug candidates for clinical trials. Still other groups have looked for allosteric inhibitors that might change protein function through binding to targeted proteins and altering an essential function. Here, also, little success has been reported. Currently NCI is funding a small number of investigators to look for inhibitors of protein/protein interaction using a series of approaches. Because solving this problem would have such a large impact in the development of new cancer therapies, this question is included to continue driving the field’s quest for new and unusually creative approaches to inhibit these traditionally “undruggable” targets. Feasibility: This question seeks new ideas to develop approaches for drug development for protein/protein interactions or other non-enzymatic inhibition of oncoprotein function. Implications of success: New classes of drugs designed to block the actions of these refractory targets would provide a wide range of opportunities for cancer treatment and prevention. |
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