Abstract

I will review progress made and remaining unmet need in cancer treatment. Key developments that I will highlight are the evolution from cytotoxic chemotherapy to molecularly targeted agents and immunotherapy. I highlight the major challenge that we face in the clinic is cancer heterogeneity, adaption and evolution to generate more aggressive and drug resistant disease. I will assess the technological advances that have enabled modern cancer drug discovery and those that will accelerate progress in the future. I will illustrate these points using examples of the successes in drug discovery we have achieved in the CRUK Cancer Therapeutics Unit at ICR. Since 2005 we have discovered 20 preclinical development candidates, progressed ten of these into the clinic, and seen our prostate cancer drug abiraterone approved for the treatment of men with prostate cancer around the world. I describe in more detail the very recent example of discovering inhibitors of the HSF1 pathway based on mechanism-based phenotypic screening. I will also emphasize the importance of high-quality chemical probes for target validation, demonstrating druggability and use as pathfinder molecules. I will stress how biologists need to choose their chemical probes wisely for use in biomedical research and describe the resources that we have built and made publicly available, including canSAR and Probe Miner, together with the Chemical Probes Portal that we are now hosting and developing further at ICR.