ProfessorGuido Franzoso, MD PhD

Professor Guido Franzoso

Chair of Inflammation and Signal Transduction

Faculty of Medicine, Imperial College London

Translating NF-κB biology into first-in-class cancer therapeutics

Professor Franzoso holds the Chair of Inflammation and Signal Transduction in the Faculty of Medicine at Imperial College London. He is an Honorary Consultant at Imperial College Healthcare NHS Trust and co-Lead of the Immuno-Pathology Network, which fosters multidisciplinary collaboration across Imperial College London, the Institute of Cancer Research (ICR), the Francis Crick Institute, and the Wellcome Sanger Institute.

Professor Franzoso obtained his medical degree summa cum laude from the University of Padua in 1987 and a Ph.D. in Microbiological Sciences from the same institution in 1993. Following clinical practice as an Internist, he moved to the National Institutes of Health (NIH) in Bethesda, where he trained as a molecular biologist. There, he conducted pioneering research in the then emerging NF-κB field, contributing to the early definition of NF-κB as a central regulator of inflammation, immunity, and cell survival. In 1997, he was appointed Assistant Professor at the University of Chicago and was subsequently promoted to Associate Professor with tenure. In 2007, Guido Franzoso joined Imperial College London as Professor and Chair of Inflammation and Signal Transduction and as Director of the Centre for Molecular Immunology and Inflammation (CMII).

Professor Franzoso’s research focuses on the NF-κB signalling pathway – a nodal transcription factor network driving inflammation and cancer – with the explicit aim of translating fundamental biological insights into clinically actionable therapeutic strategies. His work integrates molecular medicine and functional genomics to identify disease-relevant NF-κB dependencies, enabling the development of targeted interventions, companion biomarkers, and mechanistically novel therapeutics that harness the extensive translational potential of the NF-κB pathway.

His research in oncology and cancer biology has led to multiple first-in-class translational advances, spanning target discovery, drug development, and early-phase clinical trials. He has received several awards for his basic and translational research. He holds seven patents.

Current Research Programmes

• From target discovery to human trials

Translational clinical development of first-in-class NF-κB-targeted therapeutics and companion predictive biomarkers in multiple myeloma (MM) and diffuse large B-cell lymphoma (DLBCL).

Status / Highlights:

– Phase I clinical trial completed

– Clinical proof of efficacy (e.g. objective very good partial response; VGPR) at tolerable doses in heavily refractory patients (Phase I)

– Cancer cell-selective mechanistic specificity at clinically effective doses

– Phase II trial ongoing

• Cancer metabolism and precision medicine

Drug development and companion biomarker discovery in advanced colorectal carcinoma (CRC) – with a focus on microsatellite-stable/mismatch repair-proficient (MSS/pMMR) disease – and other hard-to-treat malignancies.

Status / Highlights:

– Lead optimisation

– Proof-of-mechanism and on-target selective specificity established

– Potent therapeutic efficacy with target engagement and no observable toxicity

– Validated in clinically relevant models of primary human MSS/pMMR disease (ex vivo and in vivo)

• Innate anti-cancer immunotherapy

Target identification, medicinal chemistry, and biomarker discovery in high-grade serous ovarian carcinoma (HGSOC) and additional oncological indications.

Status / Highlights:

– Target discovery

– Established in vivo conversion of immunologically “cold” tumours into cytotoxic T-cell-inflamed (“hot”) states exhibiting abundant tertiary lymphoid structures (TLSs)

– Tumour stratification and immune-checkpoint pathway refinement ongoing

– Therapeutic strategy designed to bypass resistance to immune-checkpoint immunotherapy

Further details on current research programmes are available in the Research section.

For information on the clinical, commercial, and investment opportunity around the first-in-class clinical candidate, DTP3, please visit the dedicated page on the Imperial.Tech website.

Selected publications

• De Smaele et al. (2001) Nature

• Zazzeroni et al. (2003) Blood

• Papa et al. (2004) Nature Cell Biology

• Pham et al. (2004) Cell

• Papa et al. (2008) Journal of Clinical Investigation

• Mauro et al. (2011) Nature Cell Biology

• Tornatore et al. (2014) Cancer Cell

• Verzella et al. (2018) Cancer Research

• Capece et al. (2021) Journal of Clinical Investigation

• Chaidos et al. (2025) Blood