In recent years, oncology has made great strides not only in cancer treatment but also in prevention and early diagnosis. Within this context lies the innovative strategy of cancer interception, which aims to block the progression of precancerous lesions before they turn into tumors. This approach goes beyond early detection — it seeks to intervene at the root of the problem, altering the course of the pathological process through targeted therapies.
It is in this direction that the APHRODITE study positions itself — a new clinical project supported by the Clinical Innovator Award from the prestigious Cancer Research Institute of New York and coordinated byHumanitas Research Hospital. The study will begin in the fall across five centers in Italy. With an ambitious goal — to intercept tumor transformation before cancer develops — the project, recently approved by AIFA and also supported by Fondazione AIRC, which funded the research behind the study, will test for the first time a local immunotherapy approach in patients with potentially malignant oral lesions. At the core of the study is a drug that activates the CD40 receptor and stimulates a targeted immune response.
Leading the project are Paolo Bossi, oncologist and head of the Head & Neck Cancer Section at Humanitas and professor at Humanitas University, and Enrico Lugli, director of the Laboratory of Translational Immunology. Their collaboration represents a concrete example of translational research, in which the dialogue between clinic and lab allows scientific discoveries to be translated into innovative therapeutic tools. Supporting them as co-investigators are key Humanitas professionals such as Luigi Lorini, Giuseppe Mercante, Alberto Paderno, and Maria Rescigno — experts in their respective clinical and research fields — who further enrich the multidisciplinary nature of the project.
Oral Cavity Cancer: A Often Forewarned Threat
Oral cavity cancer remains a challenging disease to treat, with five-year survival rates that, in advanced cases, do not exceed 50–60%. However, the disease can be preceded by early warning signs: so-called oral potentially malignant disorders (OPMDs) can precede the development of cancer by several years. Although not yet cancerous, these lesions carry a significant risk of malignant transformation, with more than 50% of cases eventually evolving into cancer. Even after surgical removal, the possibility of progression to malignancy cannot be ruled out.
The APHRODITE study specifically targets these at-risk patients, at a stage when the intervention can still be preventive in nature. Participants will receive a localized treatment, involving direct injection of the drug into the lesion. They will also undergo advanced immunological and molecular screening techniques conducted by Enrico Lugli’s team to identify the mechanisms underlying the anti-tumor immune response. While CD40 stimulation has already been tested in immunotherapy clinical trials, this is the first time it is being used in a preventive setting, with the aim of blocking malignant transformation at an early stage. The oral cavity was chosen not only because precancerous lesions are easily visible and accessible, but also because preclinical evidence has shown a role for CD40 receptor activation in stimulating immune responses during the early stages of disease.
As Paolo Bossi explains, the goal is to “activate an immune response directly within the at-risk tissue, before the tumor becomes clinically evident. We want to intervene early, leveraging the immune system’s ability to recognize and destroy abnormal cells before they turn into cancer. It’s an innovative approach that could revolutionize how we deal with these lesions, offering patients a less invasive and more targeted option compared to surgery.”
The phase II exploratory trial will involve about 27 patients: a relatively small number, but sufficient to gather useful data to guide larger future studies. Humanitas, as the coordinating center, will be joined by several major Italian institutions, including ASST Santi Paolo e Carlo, the European Institute of Oncology, ASST Sette Laghi, ASST Lariana, the University of Naples Federico II, and the University of Bologna.
Translational Research: Where Lab and Clinic Meet
A distinctive aspect of the project is the integration between clinical trial and deep profiling: each patient will be studied in detail using cutting-edge technologies available at Humanitas, as Enrico Lugli highlights. “Our goal is not just to evaluate the drug’s efficacy, but to deeply understand how it works and in which patients it can offer the greatest benefit. Thanks to technologies such as proteomics, metabolomics, and high-dimensional cytometry, we can analyze the immune system’s response in detail, identify predictive biomarkers, and further personalize therapy. This is the essence of precision medicine and the fundamental value of translational research: turning scientific discoveries into concrete tools to improve patients’ lives.”
Ultimately, APHRODITE is much more than a clinical trial. It is the result of a shared effort between clinicians and scientists and a concrete example of how translational research can transform scientific insight into real therapeutic opportunities. From understanding biological mechanisms to applying them directly to patients, this study shows how crucial the ongoing dialogue between lab and clinic truly is. It is precisely on this integration that the future of precision medicine is being built — a medicine that not only treats, but above all, prevents.
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3,400 Physicians
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110,400 Annual surgeries
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190,400 Annual Inpatient Admissions
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928,000 Patients
