Ten years ago, a meeting in Milan between a biologist and a urologist led to the start of a project aimed at reducing bladder cancer recurrence after surgery. Despite following all medical guidelines, many patients experience cancer returning due to residual cells too small for surgeons to detect during operations.
Dr. Massimo Alfano, group leader at the Department of Urology at Ospedale San Raffaele and coordinator of the PHIRE project, has focused his work on bridging laboratory research with patient care. "Although the urologists follow the guidelines, there is always some residual disease that remains," Massimo says. This challenge inspired two European projects: EDIT and PHIRE, both funded by the European Innovation Council (EIC).
PHIRE builds on earlier research from the EDIT project and seeks to help surgeons find cancerous tissue invisible to the naked eye. Around 2016, Dr. Alfano began investigating photoacoustic imaging—a technique combining optical imaging with ultrasound—to detect tumours smaller than one millimetre. Photoacoustic imaging works by converting light absorbed by specific molecules into ultrasound signals that can be picked up for high-resolution images.
To make this approach effective for bladder cancer, PHIRE developed engineered gold nanorods that bind specifically to markers found on bladder cancer cells. When illuminated with near-infrared light, these nanorods produce strong ultrasound signals, making it possible to detect very small tumour remnants.
Building an effective consortium was challenging for Dr. Alfano and his team. "To construct a consortium that could provide an answer to the medical need was not easy," he recalls. The final team brought together physicians, biologists, chemists, mathematicians and imaging specialists from across Europe.
Effective communication proved essential within such a multidisciplinary group and also when applying for funding. Initial grant applications were unsuccessful until clearer explanations helped reviewers understand their goals. Eventually, both Pathfinder and Transition grants were secured from EIC.
PHIRE’s innovation centers on two components: urine-stable targeted gold nanorods developed by Mauro Comes Franchini's group at University of Bologna and a new molecular imaging device created by teams led by Jithin Jose (Fujifilm Visualsonics) and Viktor Popov (Ascend Technologies). Both elements were independently evaluated by the European Commission’s Joint Research Centre; the imaging device received a "Very High Market Creation Potential" rating while the gold nanorods were rated as having "High Market Creation Potential."
The technology has been validated in animal models and recognized through patents and media coverage in scientific journals like PNAS and Advanced Healthcare Materials as well as Italian television.
Looking ahead, PHIRE aims first to complete its current phase successfully before moving towards clinical trials. The team is preparing for commercialization through a spin-off company with support from business partners including Francesca Natali, Marco Franchin and Elizaveta Kuzmina from META Group as well as Michela Cristofolini and Maria Girelli from Ospedale San Raffaele.
"When they told me I had to become an entrepreneur, I asked, what is an entrepreneur?" Massimo admits with a smile.
Coordinating such projects demands significant effort: "I spend the weekends working," he says openly. However, Dr. Alfano believes only large consortia can address complex health problems effectively: "Only a consortium can provide good answers," he states.
The next step will involve translating these laboratory advances into clinical practice—requiring further collaboration with industry partners and investors so that patients may ultimately benefit from this technology.
