Precision Oncology and Systems Biology Program

The overarching goal of the Precision Oncology and Systems Biology (POSB) Program is to leverage advanced experimental and computational tools for system-wide analysis of cancer to discover new targets, predict outcomes, and translate findings through investigator-initiated clinical trials. Identifying novel cancer therapies requires systems-level analysis of the molecular, cellular, and physiologic processes underlying tumor initiation, metastases, and drug resistance. The POSB Program brings together multidisciplinary teams with expertise in experimental and computational systems biology, translational science, and clinical oncology to solve these complexities and advance the Herbert Irving Comprehensive Cancer Center’s (HICCC)’s strategic focus on accelerating translation of discoveries to innovative clinical and population science research. Led by Peter Sims, PhD, Kenneth Olive, PhD, and Gulam Manji, MD, PhD, the Program’s 43 Members broke new ground during the project period in pre-clinical studies targeting chemotherapy-resistant cell populations, modeling metastatic events previously inaccessible in animal models, and developing new drug screening platforms. POSB Program physician-scientists and systems biologists collaborated to translate pre-clinical findings and bring genomic analyses and computational modeling to investigator-initiated trials. In 2024, Program Members held $15M in cancer-focused, peer-reviewed funding (Annual Direct Costs, increased 40% since the last submission), including $6.1M (41%) from NCI, $6.5M (44%) from other NIH sources, and $2.1M (15%) from other peer-reviewed agencies, and authored 454 cancer-relevant research publications, including 179 (39%) inter- and 75 (17%) intra-programmatic, with 20% in journals with impact factors >20 and 40% (of total) with impact factors >10 (all metrics increased since the last submission). POSB clinical investigator-led trials included 934 interventional enrollments of which 45% to investigator-initiated trials. The POSB Program has interrelated Specific Aims: (1) Advance systems approaches to translational therapeutics using preclinical models and computational approaches to elucidate the mechanisms of tumor initiation, plasticity, metastasis, and therapeutic response and define the mechanisms of novel and existing drugs through their effects on both malignant and stromal cells, and on cell state transitions; (2) Advance translational and clinical systems oncology by developing novel clinical trial endpoints using systems biology and single-cell genomics and by interrogating tumor biology through systems-based analyses of clinical trial samples. The HICCC has provided over $16M in support for POSB recruitments, pilot funding and resources to foster the Program’s needs within the HICCC’s Strategic Plan. Over the next project period, POSB will continue to grow the robustness, vibrancy, and impact of its research by enhancing the experience of junior researchers; tackling areas of unmet needs where systems biology has been under-utilized; expanding technologies in genomics and systems immunology; and leading ground-breaking clinical trials that translate and incorporate systems biology.