Epigenetics, transcriptomics, and metabolism represent the hidden architects of cancer evolution and survival. These unseen forces — which orchestrate how genes are silenced, expressed, or fueled — offer a new dimension of precision in cancer treatment, far beyond the scope of traditional chemotherapies. This morning’s joint Scientific Program session, Emerging Therapeutic Strategies Targeting Epigenetic, Transcriptomic, and Metabolic Mechanisms (9:30 a.m. – 11:05 a.m., Convention Center, Room 24), is set to spotlight the bold advances in exploiting the vulnerabilities within cancer’s molecular architecture.
A collaboration between ASH’s Scientific Committee on Epigenetics and Genomics and Scientific Committee on Myeloid Neoplasia, the session will explore the potential of omics-driven therapies. “Our committees recognized the need for a session on novel therapeutic approaches, and after discussions at last year’s ASH meeting, we decided to collaborate,” said session co-chair Dinesh S. Rao, MD, PhD, from the University of California Los Angeles. “Our committee has long been at the forefront of genomics and epigenetics research, and the convergence of new high-throughput technologies with these insights has led to therapeutic developments that were unimaginable just a few years ago. This session was designed to bring these innovations to the forefront.”
Hannah J. Uckelmann, PhD, from the Frankfurt Cancer Institute in Germany, will discuss her work targeting transcriptional mechanisms in acute myeloid leukemia (AML). NPM1 mutations, which occur in about one-third of AML cases, play a key role in leukemogenesis. Dr. Uckelmann discovered an unexpected role of mutant NPM1 on chromatin, providing the molecular basis for targeted epigenetic therapies in NPM1-mutated AML. Her work led to the inclusion of patients with NPM1-mutated AML in the ongoing clinical phase II trials for menin-MLL inhibitors.
Gerald R. Crabtree, MD, from Stanford University, will describe proximity-inducing molecular glues and heterobifunctional molecules that can modulate challenging therapeutic targets in novel ways. His team has devised transcriptional/epigenetic chemical inducers of proximity, molecules that don’t simply block cancer signals but also “rewire” the genes to trigger self-destruction — an innovative strategy with huge potential for therapeutic breakthroughs. They focused on diffuse large B-cell lymphoma, where the BCL6 transcription factor is often deregulated. The team’s approach reprogrammed BCL6 to activate genes that promote cell death in lymphoma cells, without causing any side effects in healthy mice.
Benjamin Cravatt, PhD, from the Scripps Research Institute, is scheduled to discuss the untapped potential of RNA-binding proteins — molecules once thought to be impossible to target with drugs.
Lastly, Courtney Jones, PhD, from Cincinnati Children’s Hospital, will explore metabolic dependencies in leukemia, focusing on AML and leukemic stem cells. “In leukemia metabolism, we are seeing a wave of new therapeutic options being tested or poised for clinical evaluation,” Dr. Jones said. “These studies will help us better understand how leukemic cells respond to metabolic disruptions, informing more effective treatments. As we continue to unlock the biology of leukemia, we are discovering bold new ways to target leukemic cells directly — strategies that could soon be translated into the clinic to improve patient outcomes.”
“We hope attendees gain insight into the current state of ‘drugging’ gene regulation and metabolic pathways,” said Dr. Rao. “Novel ideas, such as targeting non-enzymatic molecules and developing heterobifunctional therapies, are opening new doors for cancer treatment. We also hope this session sparks new collaborations and innovative research.”
These emerging therapeutic strategies — focused on epigenetics, transcriptomics, and metabolism — offer unique opportunities for cancer treatment. Molecules once considered "undruggable" are now being redefined as "untapped” targets, raising hope for a future where precision medicine becomes the standard of care.
