Summary
In this episode, Dr. Dan Theodorescu discusses his groundbreaking research into chromosome loss and its implications for cancer treatment and prevention. We explore the themes of convergence, community, and the human stories behind scientific discovery, highlighting how interdisciplinary efforts can lead to transformative advances in cancer biology.
Key Topics
• Chromosome loss and its role in cancer aggressiveness
• Convergence of disciplines in cancer research • The impact of Dr. Theodorescu’s research on immunotherapy
• The strategic focus on convergence to health at U of A
• The importance of community and human connection in science Takeaways
• Chromosome loss can make cancers more aggressive but also opens new treatment avenues
• Interdisciplinary convergence accelerates cancer research and innovation
• Dr. Theodorescu’s research could reshape cancer risk assessment and prevention
• Community and human connection are vital in driving scientific progress
• Dedication to patient-centered research is at the core of cancer innovation
Articles
• Beyond sex determination: the Y chromosome in male cancers | Nature | May 21, 2026 (https://www.nature.com/articles/s41568-026-00935-x)
• X and Y chromosomes as determinants of aging and disease | Science | October 1, 2026 (https://www.science.org/doi/10.1126/science.aeh0145)
Who Is Dr. Dan Theodorescu?
Dan Theodorescu MD PhD is the Nancy C. and Craig M. Berge Director of the University of Arizona Comprehensive Cancer Center. A urologic oncologist and physician scientist trained at University of Toronto and Memorial Sloan Kettering Cancer Center, Theodorescu’s pioneering convergence of cell, computational, and translational biology led to the discovery of regulators of tumor growth, metastasis, and therapeutic response.
His seminal discovery that loss of the Y chromosome, and specific genes it encodes, by tumors and immune cells drives cancer progression through immune evasion illuminated the underlying functional consequences of this long-standing genetic alteration. This represents a paradigm shifting series of discoveries with far reaching implications for immune checkpoint blockade, CAR-T cell therapies and sex specific cancer biology. His penchant for novel cancer-related discovery is also demonstrated by developing pioneering computational technologies that led to a “first in class” inhibitor to the RalGTPase, a protein involved in cancer metastasis, now in commercial development. His development of the COXEN algorithm and the revolutionary AI-driven Molecular Twin Precision Oncology Platform that creates computational replicas of patients and their tumors using tumor-host multi-omic data, introduced mechanistically grounded, predictive tools that underwent proof-of-concept clinical trials, reshaping concepts of biomarker design, drug selection, and individualized treatment. He has consistently translated his fundamental discoveries into first in class therapeutic candidates, including DDR2 directed immunotherapy sensitizers, and NPEPPS, a new target whose inhibition overcomes platinum resistance.
His laboratory has been continuously funded by the NCI soon after his first faculty appointment in 1995. In 2025 he received an R35 Outstanding Investigator Award (OIA) from the National Cancer Institute (NCI). Theodorescu has been a PI of an NCI P01 and a project leader in a SPORE as well as a current MPI and project leader U54 and P01. In 2021 he was awarded the inaugural and only national Director Award for a DOD Convergence Science Virtual Cancer Center (https://csvcc.org/).
He has elected to the American Society for Clinical Investigation (ASCI), Association of American Physicians (AAP), the American Association of Genitourinary Surgeons (AAGUS), the American Surgical Association (ASA) and the National Academy of Medicine (NAM). Theodorescu is a Fellow of the American Association for the Advancement of Science (AAAS) and served on the National Cancer Policy Forum (NCPF) of the National Academies of Science, Engineering and Medicine and on the NCI’s Board of Scientific Counselors (BSC). He is the founding co-editor in chief of Bladder Cancer, the first journal focused on this disease.
Since 2025 Theodorescu is the Nancy C. and Craig M. Berge Director of the UofA Comprehensive Cancer Center. Previously, Theodorescu was Director, University of Colorado Comprehensive Cancer Center. He led the center through two NCI Cancer Center Support Grant (CCSG P30) renewals. Under his leadership, the center was elected to the National Comprehensive Cancer Network (NCCN) and Oncology Research Information Exchange Network (ORIEN) and awarded a LAPS/NCI grant. Theodorescu worked with State of Colorado legislators to secure yearly center funding. At the federal level, he worked on parts the 21st Century Cures Act passed in 2016. He was appointed a Distinguished University Professor in 2017, one of less than 100 such individuals in the history of the University.