The ground-breaking sequencing of the first leukemia genome was presented at the American Society of Hematology Meeting in 2007. Over the next decade, there has been an unprecedented increase in the application of massively parallel sequencing to the characterization of human malignancies. While advances in technologies have profoundly deepened researchers’ knowledge of these diseases, challenges still lie ahead, such as the successful translation of next-generation sequencing approaches to the actual care of patients with cancer. Moreover, a significant number of patients lack an immediately "druggable" cancer-associated genetic alteration. Often, these patients have abnormalities of transcription factors or other historically intractable therapeutic targets. This session will focus on the application of new, cutting-edge genomic and chemistry-based approaches aimed at addressing challenges during this next phase of molecularly informed cancer therapy.
Dr. David Solit will discuss recent advances in precision oncology and the application of massively parallel sequencing to patient care. In particular, he will focus on insights gained from the study of extraordinary responders and the prospective tumor/normal profiling initiative at his institution.
Dr. Kimberly Stegmaier will discuss the application of genome-scale functional genomic screens to identify new "synthetic lethal" liabilities. This will be discussed in the context of aberrant transcription factors, including transcription factor fusions, expressed in malignancies typically lacking matched targeted therapies. One alternative approach to targeting these cancers is to identify vulnerabilities incurred by the cells in the context of the oncogenic transcription factor.
Dr. Craig Crews will discuss PROTAC-mediated protein degradation, a chemical biology concept that has successfully transitioned from the laboratory to the clinic (first clinical trials began in March 2019 for prostate cancer). This new technology has great potential to increase the druggable target space. Several hematological PROTAC targets have been successfully degraded, demonstrating the feasibility of using this new modality to treat cancers, including those hematologic malignancies driven by transcription factor fusions and other difficult drug targets.