ERA PerMed funds PORTRAIT project

The international multicenter project coordinated by IRST IRCCS thanks to a ERA PerMed funding, intends to deepen the knowledge on the interaction between microbiota, tumor, drugs and how this can be found in the volatile component of sweat

Can smell be a useful characteristic for defining personalized diagnostic and therapeutic strategies that are both effective and minimally invasive? It is precisely this distinctive property of each person, the smell, precisely, one of the keys that will be used in the international multi-center project coordinated by the Romagna Institute for the Study of Tumors “Dino Amadori” IRST IRCCS, called PORTRAIT – acronym of “A multi -omics is a non-invasive tool for the early recognition of patients with triple negative breast cancer and Her2+ responders to neoadjuvant therapy” – with the aim of identifying breast cancer patients able to best respond to a specific therapy and monitor them progress without the help of demanding tests or ineffective treatments.

The smell is given by the so-called Volatile Organic Compounds (or Volatile Organic Compounds, VOCs) which are the final result of metabolic and pathological processes, and are produced both by our body and by the microbiota. Therefore, they are able to reflect the molecular activities related to the mechanisms of tumor development. PORTRAIT, through the integration of patient characteristics (including inflammatory status) with omics data from multiple sources – genomics, transcriptomics, epigenomics, metagenomics, metabolomics and proteomics, data made available thanks to the application of sophisticated technologies – intends deepen knowledge on the interaction between microbiota, tumor and drugs, and how this can be found in the VOCs contained in sweat. A scientific challenge that would make it possible to immediately identify which therapy could be more effective for each individual person, avoiding ineffective approaches and useless side effects.

The coordinator of PORTRAIT is Dr. Francesca Pirini, biologist of the Biosciences Laboratory, who will carry on the study in collaboration with colleagues Sara Bravaccini, Michele Zanoni, Maria Maddalena Tumedei, Michela Cortesi and, for the development and management of the international consortium, Paolo Mariotti (Innovation Manager, Technology Transfer Research and Training Office) and Monica Tramontin (Technology Transfer Research and Training Office). The project sees the participation of 5 other international research centers – University of Lille (France), IRCCS Oncological Reference Center of Aviano CRO (Italy), University of Granada (Spain), University of Heidelberg (Germany), Sharett Institute for Oncology of Jerusalem (Israel) and a hi-tech company, Avalon Tecnologías de la Información Iruña (Navarre, Spain) – and will have a duration of 3 years (2023-2025). The study was worthy of a total financial support of 1,193,076 euros from ERA PerMed, a consortium co-financed by the European Commission created to promote collaborative research projects in personalized medicine.

Although the initial clinical picture is similar, women affected by the two most aggressive forms of breast cancer – triple negative (TNBC) and Her2+ – have widely different responses to standard therapy (neoadjuvant treatment). This is due to the influence of individual characteristics, among which the microbiota stands out (the set of microorganisms that coexist with the human organism). In recent years many studies have highlighted how the microbiota, both intestinal and tumoral, intervenes in the development of tumors and in the response to therapies by modulating the immune reaction and cellular metabolism. The manipulation of the microbiota could, therefore, represent a strategy to enhance the therapeutic effects of neoadjuvant treatments. Even if the interaction between tumor, microbiota (both tumor and other parts of the body) and drugs is not yet clear, the application of advanced technologies such as metabolomics and proteomics has increased knowledge on its functional role and has allowed the identification of new possible biomarkers. Among these, extremely promising, are volatile organic compounds. The detection of VOCs in various biosamples represents a recent, but specific and sensitive option for the screening of many diseases, also applicable to the monitoring of the efficacy of treatments. In this sense, the specific VOCs of the sweat of patients with breast cancer, also influenced by the microbiota, could represent a valid, non-invasive tool for the identification of patients who could respond to neoadjuvant therapies and for monitoring the efficacy of the treatment.

“In the future – comments Dr. Francesca Pirini – the results of this study could allow the development of a device which, inserted for example in a simple bra, could provide data capable of helping the clinician in choosing the most effective therapeutic strategy , and provide real-time data on tumor response to treatment, thus focusing time and resources on the best chance for each patient.”

“It is now clear that tumors are not an entity in themselves but the result of interactions with the whole organism that modify its biology and metabolism – explains prof. Giovanni Martinelli, Scientific Director of IRST -. Having set up an international consortium of great scientific value to understand how these interactions take place and how to exploit them to lighten the impact of the disease on patients by improving diagnostic and therapeutic approaches, gives this project a pioneering value in cancer therapy. I thank the Grant Office, especially Dr. Paolo Mariotti, for having helped Dr. Pirini to achieve this important, albeit initial, goal of great value for our institute”.