Julio Aguirre-Ghiso, PhD
Director, Head and Neck Cancer Basic Research
Director of Solid Tumor and Metastasis Research
Division of Hematology and Oncology, Department of Medicine and Department of Otolaryngology, Mount Sinai School of Medicine
Dr. Julio Aguirre-Ghiso - Cancer patients presumed cured after primary tumor removal and therapy, can carry non-proliferating ‘dormant’ disseminated tumor cells (DTCs) for years before reactivating to form incurable metastasis. Dr. Aguirre-Ghiso focuses on understanding the biology of dormant DTCs and their reactivation, to target them and prevent relapse. This contrasts to the vast majority of cancer research, which focuses on understanding constant cancer growth. His team led a paradigm shift that is revealing a novel cancer dormancy biology. He integrated mechanisms of basic stress and mitogenic signaling, adult stem cell and micro-environmental biology and discovered that a reciprocal crosstalk between DTCs and the microenvironment regulates the inter-conversion between dormancy and proliferation. Dr. Aguirre-Ghiso discovered that an imbalance in p38a/b and ERK1/2 signaling regulates lineage commitment transcription factors and en epigenetic network that induces dormancy. We also identified retinoic acid and TGFb2 in the microenvironment as inducers of the high p38/ERK-signaling ratio and that dormancy (quiescent phenotype) is controlled by mechanisms driving adult stem cell biology. Translating this biology to medicine he identified a “dormancy signature” enriched in dormant DTCs from patients asymptomatic for up to 18 years and that predicts for prolonged metastasis-free periods in different cancers. His work has propelled new questions to the forefront of cancer research, with the unexpected discovery that dormant DTCs can originate very early during cancer evolution, disseminating during pre-malignant stages of cancer. He has also designed an epigenetic reprograming therapy to induce dormancy of DTCs and developed a translational program with Eli Lilly to target dormant disease.