Ten years ago, a discussion in Milan set a demanding project in motion. In a meeting between a biologist and a urologist, one question kept returning: why do so many bladder cancer patients face recurrence even after surgery that follows every guideline?


The initiative highlights successful stories from projects funded by the European Innovation Council (EIC). Featured in DeepSync, part of the EIC Communities project, these stories offer a unique opportunity to connect with fellow members and innovators. By showcasing the challenges and successes of each project's journey, these stories present key moments and insights that can raise visibility, foster deeper understanding, and encourage collective knowledge exchange across communities.

Dr Massimo Alfano, group leader at the Department of Urology at the Ospedale San Raffaele, trained at the University of Milan (Italy) and coordinator of PHIRE project, has built his career around translational medicine.

His work begins with patients and clinicians, not only with laboratory hypotheses. “The focus of my research is to give some answers to the patients,” he explains. “We start from unmet clinical needs and try to give something back.”

In bladder cancer, the unmet need is clear. Surgeons remove what they can see; however, cancer cells smaller than one millimetre often remain. These tiny traces, invisible during surgery, can resist therapy and lead to the disease returning. “Although the urologists follow the guidelines, there is always some residual disease that remains,” Massimo says. This gap between what is visible and what is left behind became the driving force behind two European projects: EDIT and then PHIRE.

The first major step came in 2018, when Massimo coordinated the EIC Pathfinder project EDIT. PHIRE, the current EIC Transition project, builds directly on those results. Both are dedicated to bladder cancer and share the same ambition: to allow surgeons to detect what they cannot currently see.

The scientific path was neither quick nor obvious. Around 2016, Massimo began exploring how tumours smaller than one millimetre might be detected. He reviewed the literature and spoke with researchers across Europe. Eventually, he focused on photoacoustic imaging.

Photoacoustic imaging is a hybrid technique that converts light into ultrasound. When specific molecules absorb laser light, they undergo rapid thermoelastic expansion and generate ultrasonic waves that can be detected. This approach combines the contrast advantages of optical imaging with the depth penetration of ultrasound, enabling high resolution visualisation, down to one tenth of a millimetre — suitable for detecting very small lesions.

However, tumour tissue doesn't inherently generate a strong photoacoustic signal for reliable detection. To address this, PHIRE has developed engineered gold nanorods, designed with a precise shape, to bind selectively to molecular markers expressed by bladder cancer cells. Due to their optical properties, these nanostructures strongly absorb near-infrared light and convert it into ultrasound signals upon laser illumination, enhancing contrast and enabling the detection of small residual tumour areas This combination of high-resolution imaging and tailored contrast agents defines the originality of PHIRE.

Identifying the correct partners was one of the hardest stages. Massimo spent six months contacting researchers and companies across Europe. Many were not the right fit. “To construct a consortium that could provide an answer to the medical need was not easy,” he recalls. Difficult decisions had to be made.

The final consortium includes physicians, biologists, chemists, mathematicians and imaging specialists. Their different backgrounds make the project strong but also complex. “The partners all speak different scientific languages,” Massimo says. A mathematician does not automatically understand medical priorities, and a clinician may not follow complex modelling discussions. The coordinator’s role is to keep everyone aligned and focused on the same goal.

Communication became as important as the experiments themselves. The team learned to avoid technical jargon and to explain the medical problem in clear terms. This was especially important when submitting proposals and facing external reviewers, who may not share the same expertise. The first application was not funded immediately. Reviewer comments were sometimes frustrating, occasionally revealing misunderstandings. Yet persistence and clearer communication made the difference. The Pathfinder grant arrived only at the third submission, and the Transition grant at the second submission.

PHIRE’s innovation rests on two central elements: the innovative i) urine-stable targeted gold nanorods by the group lead by Mauro Comes Franchini from University of Bologna (Italy), acting against bladder tumour markers, and ii) novelmolecular imaging device by the groups led by Jithin Jose (Fujifilm Visualsonics, Netherlands) and Viktor Popov (Ascend Technologies, United Kingdom), forming the preclinical imaging platform. Both components were independently evaluated by the European Commission’s Joint Research Centre using the Market Creation Potential framework. The imaging device was rated “Very High Market Creation Potential,” and the gold nanorods “High Market Creation Potential.”

In May 2025, PHIRE was highlighted as pioneering work during the European Week Against Cancer. The technology has been documented in high-impact scientific journals (PNAS, Advanced Healthcare Materials) and even featured in Italian media, including a television report by TGCOM. These milestones underscore not only the originality of PHIRE, but also its relevance beyond the laboratory.

The technology works effectively in animal models, detecting tumours far smaller than one millimetre. Patents have been secured for the contrast agent, and recognition by European innovation evaluators confirms its potential.

The short-term goal is to complete the PHIRE project successfully, ensuring that all partners deliver their contributions on time. “Even negative results are results,” Massimo stresses. Learning from failed experiments is part of the process.

The long-term objective is more ambitious: moving from laboratory validation to clinical application. The team is preparing the ground for a spin-off company, seeking investment and planning future clinical trials. This stage requires skills that are not traditionally part of scientific training.

“When they told me I had to become an entrepreneur, I asked, what is an entrepreneur?” Massimo admits with a smile. Business models and market strategies are new territory. Partners with expertise in exploitation and communication, including Francesca Natali, Marco Franchin and Elizaveta Kuzmina from META Group and colleagues Michela Cristofolini and Maria Girelli from Ospedale San Raffaele working closely on the business side, are playing a key role. The business model has evolved during the project as new results emerged, showing how innovation rarely follows a straight line.

Coordinating PHIRE has had a direct impact on Massimo’s daily life. “I spend the weekends working,” he says openly. Beyond his own laboratory research, he reviews deliverables, organises meetings and supports partners across disciplines. The responsibility is significant, and the workload constant.

Yet he remains enthusiastic. Large European projects, he believes, allow complex problems to be addressed from multiple angles. Smaller grants often limit work to a single laboratory perspective. “Only a consortium can provide good answers,” he says. Tackling bladder cancer requires expertise in biology, chemistry, imaging, mathematics and clinical practice working together.

PHIRE is not simply a technical development; it reflects a way of working that connects scientific curiosity with patients' needs. The path has included rejections, misunderstandings, long evenings and new responsibilities. It has also brought patents, recognition and the possibility of real clinical impact.

For others considering a similar journey, the message is clear. Research is demanding and often uncertain. It requires patience, collaboration and a willingness to learn beyond one’s own discipline. But when the goal is to improve patient care, the effort carries a meaning that goes far beyond the laboratory.

The next step is to translate the technology into clinical practice. This will require not only scientific commitment, but also entrepreneurial partners and investment. For PHIRE to move from promising laboratory results to real benefits for patients, collaboration with industry and innovation stakeholders will be essential.


Photo credits:
Photo credits: PHIRE project



Contacts:
Project coordinator: APRE
Stefania De Santi, desanti@apre.it

Communication Team: Fondazione ICONS
Cesar Giovanni Crisosto – cesar.crisosto@icons.it
Caterina Falcinelli – caterina.falcinelli@icons.it

Project website: https://deepsync.eu
LinkedIn: DEEPSYNC