Tumor Metastases: How They Develop, Pre-clinical Models to Study Them, and Novel Therapeutic Strategies for Their Treatment
Alessandro Fatatis MD, PhD
Professor of Pharmacology, Physiology and Pathology
College of Medicine
Dissemination and growth of primary tumors to distant sites generate secondary metastatic tumors that dramatically worsen patients’ prognosis. For instance, very few patients, in any, succumb to locally confined prostate and breast cancer, whereas the approximately 15 to 30% that would eventually develop metastatic disease from these tumors are currently treated, but not cured. Metastasis require the successful execution of a cascade of events, from the entry of cancer cells into the systemic circulation to the colonization and growth in tissues different from those in which the primary tumor originally emerged. The identification of therapies more effective than the ones currently available requires pre-clinical modeling of human disease in a clinically relevant fashion, leading to an improved understanding of the functional interactions among tumor and normal cells, and the genetic and molecular factors underpinning such interactions.
Our laboratory is actively involved in identifying molecular mediators of metastatic behavior that will serve as novel therapeutic targets. We use a combination of animal models that faithfully reproduce the metastatic process in humans, allowing us to visualize cancer cells immediately after their arrival to different organs (seeding) via the blood circulation, and also to follow their progression into tumors using longitudinal in vivo imaging. Molecular analyses are then performed on cancer cells following their seeding, by collecting them from the blood of tumor-bearing animals and finally by harvesting both metastatic tumors and surrounding normal tissues using Laser Capture Microdissection. This combination of approaches led us to identify potential therapeutic targets for which novel antagonists have been generated or existing therapeutics could be repurposed.
Alessandro Fatatis, MD, PhD, is an experimental oncologist and professor in the Department of Pharmacology and Physiology at Drexel University College of Medicine and is the co-leader of the Program in Prostate Cancer at the Sidney Kimmel Cancer Center of Thomas Jefferson University. Dr. Fatatis works on solid tumors, in particular prostate and breast cancers, with a strong focus on the identification of novel therapeutic targets for metastatic disease.