Label-Free Raman Approaches for Patient-Specific Biochemical Tumor Mapping to Monitor Personalized Anticancer Resistance Simulation

RAMPART aims to address the significant clinical challenge of tumor resistance to anticancer therapies, a key factor contributing totreatment failure and decreased patient survival, particularly in Head and Neck Squamous Cell Carcinoma (HNSCC). The project’sprimary objective is to develop a label-free, nondestructive and rapid methodology using Raman and multimodal imaging to identifybiomarkers of tumor resistance, by monitoring the biochemical responses of ex vivo patient-derived tumor slices to both immunotherapyand radiotherapy.To do so, RAMPART will employ cutting-edge Raman spectroscopy, including both spontaneous (SR) and a multimodal microscope(SRS-TPEF-SHG), to perform high-resolution biomolecular mapping and imaging of patient-derived tumor samples. This approachallows for precise detection of biomolecular changes within the tumor microenvironment (TME), offering a comprehensiveunderstanding of the factors driving therapy resistance. The project will be conducted at Politecnico di Milano (main host), and twosecondments at Jena University Hospital (UKJ) and Johns Hopkins University (JHU), where I will prepare patient-derivedHNSCC slices.The relevance of RAMPART lies in its potential to significantly enhance clinical decision-making in HNSCC oncology,advancing the state-of-the-art in tumor evaluation, with label-free and nondestructive approaches for biomolecular tumor imaging.By establishing a protocol for the early detection of resistance biomarkers, the project will enable rapid, personalized treatmentstrategies tailored to individual patients, driving to decision-making time of 5-7 days. Additionally, the insights gained into tumorheterogeneity and the TME will contribute to a more profound understanding of their roles in treatment outcomes. The project’sfindings are expected to potentially impact on the field of precision medicine, ultimately improving survival rates and qualityof life for patients with HNSCC.