We propose a general strategy in cancer drug discovery that has the potential to generate more accessible and highly effective anti-cancer compounds than other known strategies. Our approach is an innovative twist on two existing methods: 1. High throughput screening enables scientists to perform phenotypic screens on hundreds of thousands of compounds at a time, leading to the discovery of novel biological targets and the identification of chemical starting points for developing new cancer drugs. 2. The development of drugs that eliminate key cancer proteins and selectively cause the death of tumor cells (“protein degraders”) has the potential for treating many forms of cancer. The discov...

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We propose a general strategy in cancer drug discovery that has the potential to generate more accessible and highly effective anti-cancer compounds than other known strategies. Our approach is an innovative twist on two existing methods: 1. High throughput screening enables scientists to perform phenotypic screens on hundreds of thousands of compounds at a time, leading to the discovery of novel biological targets and the identification of chemical starting points for developing new cancer drugs. 2. The development of drugs that eliminate key cancer proteins and selectively cause the death of tumor cells (“protein degraders”) has the potential for treating many forms of cancer. The discovery of these anti-cancer protein degraders is conducted in a methodical, biased and time-consuming manner that relies on our current knowledge of cancer biology (which is limited) and on the availability of known anti-cancer compounds that have been reported in the literature (which reflects a narrow subset of all possible cancer drugs). There is great potential in developing an unbiased approach for the high throughput discovery of novel protein targets for cancer and their corresponding anti-cancer protein degraders using phenotypic screening, which would leverage the benefits of high throughput screening to generate a diverse library of protein degraders. We propose a novel platform for creating anti-cancer protein degraders that can be integrated into existing large libraries of unbiased compounds in academia and industry. If successful, this research program will provide an innovative, accelerated approach for the high throughput discovery of new protein degrader-based treatments for a broad range of cancer types. We will conduct proof-of-concept studies to generate new compounds that selectively kill cell lines derived from lung cancer and pancreatic cancer. In the long-term, our proposal has the potential to impact many types of cancer in an unbiased manner.

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