Genome-inspired Cancer Drug Discovery

Cancer is a disease of the genome. Cancer cells carry different genomic alterations compared to normal cells, many of which are prime targets for effective anti-cancer therapies. Currently there is no therapeutic approach for many of the most common genome alterations—among them alterations in MYC, p53 and telomerase. Much of our work in the Meyerson lab is focused on advancing efforts to develop and improve new and existing cancer therapies.
 
Our work on telomerase has led to a clear analysis of the indications for telomerase inhibition in the treatment of glioblastoma based on cell line and xenograft dependency (Aquilanti et al., 2023), as well as a potential framework for further discovery of small molecule inhibitors of telomerase (Aquilanti et al., 2025). Further efforts have yielded a screening method for potential inhibitors of telomerase which has identified 2 compounds with a direct inhibitory effect on telomerase. Furthermore, our work with SLFN12 and PDE3A in glioblastoma has also led to the discovery that velcrin molecules can selectively kill glioblastoma cells with high SLFN12 and PDE3A expression levels (Aquilanti et al., 2024).

Recent collaborative efforts on p53 have led to an approach capable of inducing cell death in p53 mutant cells via small molecules, a promising and novel avenue for the treatment of all p53 mutant cancers (Sadagopan et al., 2025). The approach uses the increased concentration of p53 protein in these mutant cells, enabling small molecules to bind to a specific protein change and pool PLK1 inhibitors to induce selective cell death. This method potentially provides an avenue for robustly targeting p53 abundance in cancer cells, opening new doors for drugging the most commonly mutated gene in cancer.
 
As part of our efforts to advance the treatment of non small-cell lung cancer, in collaboration with Bayer, we have successfully worked to develop a novel targeted therapy, sevabertinib, for the treatment of NSCLC with somatic ERBB2 mutations (Siegel et al., 2026). As of November 19th, 2025, the FDA has granted accelerated approval of sevabertinib for the treatment of advanced NSCLC. Learn more about this exciting achievement from the Broad Institute press release and Q&A with Matthew Meyerson and Heidi Greulich, the Dana-Farber press release, The Harvard Crimson, and the Bayer Pharmaceutical press release!