Carlo V. Catapano, MD, PhD, is the Director of the Institute of Oncology Research (IOR), Director of Laboratory of Experimental Therapeutics, and Head of the Tumor Biology and Experimental Therapeutics program. Dr. Catapano received the MD degree summa cum laude from the University of Naples (Naples, IT) in 1983. He specialized in Oncology at the University of Naples in 1986. Then he continued his post-graduate training in cancer pharmacology at Mario Negri Institute for Pharmacological Research, IRFMN, in Milan, IT, and in biochemistry and molecular biology at the Wake Forest University (WFU) and Bowman Gray Comprehensive Cancer Center in Winston-Salem, NC, USA, where he received in 1993 the PhD in Biochemistry. From 1993 to 2003, he was Professor at the Medical University of South Carolina (MUSC), Charleston, SC, USA, with joint appointments in the Departments of Experimental Oncology, Biochemistry and Molecular Biology, and Medicine (Hematology/Oncology). He was also senior member of the MUSC Hollings Cancer Center, the Center for Molecular and Structural Biology and the Laboratory of Cancer Genomics. In 2003, Dr. Catapano moved to Switzerland where he was the Director of the Laboratories of Experimental Oncology of the Oncology Institute of Southern Switzerland (IOSI) and then, from 2011, is the Director of the IOR. His team works at the discovery and development of novel therapeutic strategies focusing on the epigenetic regulatory mechanisms that underline the pathogenesis and progression of human cancers.
The overall objective of the research conducted by the team is the discovery of innovative strategies for treatment of cancer based on a deep knowledge of the complex interplay between the epigenetic, transcriptional and metabolic processes underpinning cancer development.
Defining the role of epigenetic regulators and the potential of epigenetic therapies.
Extensive reprogramming of the epigenetic landscape occurs in tumor cells during the progression to metastatic and treatment-resistant states. The group is studying the contribution of epigenetic mechanisms to disease progression, and the potential of drugs targeting specific epigenetic effectors to prevent or revert the acquisition of treatment-resistant traits. The laboratory has identified epigenetic regulators (e.g., BRD4, EZH2, KDM1A) that are overactive in human cancers and has tested the ability of their genetic knockdown and pharmacological inhibitors to counteract tumor cell plasticity and treatment resistance. The integration of multiple experimental approaches and model systems has given relevant insights. Along this line, the team is currently exploring in various preclinical models of prostate and liver cancer the activity of epigenetic drugs with the intent to increase efficacy and reduce treatment failures. In an ongoing SNSF-funded project, the group is integrating these novel concepts of epigenetic therapy with nanomedicine-based approach for tumor-targeted combinatorial delivery of multiple anticancer drugs with increased efficacy and reduced toxicity.
Cancer stem cell and novel therapeutic approaches.
Tumor cells with stem-like properties, called cancer stem cells (CSCs), are recognized as the major responsible of disease recurrence, metastasis and treatment failure. Novel effective CSC-directed therapies may establish a new paradigm in cancer treatment. The team has developed experimental methods and models to study the CSC subpopulation in tumors and test the effects of genetic and pharmacological interventions. Using these systems, along with genomic data from clinical samples, the laboratory explored the pathways that drive the expansion and maintenance of CSCs in human cancers. A major recent finding is the close interplay between epigenetic and metabolic pathways in CSCs. The group has recently defined mitochondria as a central hub in these stem cell-related processes and has identified key targets in mitochondrial dynamics and turnover that offer new promising avenues for drug discovery and development. Notably, these processes represent a critical vulnerability for CSCs and can be exploited therapeutically to induce their progressive exhaustion and elimination. These concepts are at the basis of ongoing SNSF and KLS funded projects.