Scientific Leads:
Appetecchia Marialuisa, Ciuffreda Ludovica, Melucci Elisa, Cutillo Giuseppe, Marchesi Francesco

Description

This research line is aimed at developing and implementing novel personalised-medicine approaches in oncology based on the biological and molecular characteristics of tumours, while promoting the integration of sex- and gender-sensitive medicine models. Preclinical and clinical projects will focus on advancing and translating into clinical practice new models of care that integrate tumour characteristics with innovative diagnostic and therapeutic approaches, taking into account each individual’s previous clinical history and differences related to age, sex and gender. In this context, basic research aimed at improving the understanding of tumour pathogenesis and heterogeneity is of major relevance, as are innovative clinical trials based on improved stratification of patient groups selected according to specific biomarkers and health determinants. The study of the molecular mechanisms responsible for tumour pathogenesis and progression is enhancing our understanding of tumour heterogeneity at both the inter-individual and intra-individual levels, as well as its evolution over time. Omics-based molecular diagnostics and imaging are transforming tumour classification and staging and opening new avenues for targeted therapeutic approaches. Accordingly, this research line will include molecular-biology studies enabling a more accurate characterisation of the mechanisms underlying tumour pathogenesis and progression, a deeper understanding of intra- and inter-individual tumour heterogeneity, and the development of personalised therapies tailored to each patient. Molecular diagnostics relies on the integration of different approaches, including liquid biopsy. When combined with information on the molecular profile of the primary tumour, liquid biopsy allows the sensitive and non-invasive analysis of circulating tumour cells, circulating tumour DNA (ctDNA), and circulating tumour RNAs (including miRNAs and circRNAs), with the ultimate aim of monitoring disease, adapting therapeutic strategies, and developing novel treatments based on agents that specifically interfere with cellular pathways responsible for tumour growth, survival and progression. This framework also encompasses sex- and gender-sensitive medicine, which recognises that biological and sociocultural differences influence health status, disease, and individual responses to treatment. Genetic, epigenetic, physiological and environmental factors - including sex, age, exposure to pollutants, diet, smoking and alcohol consumption - have been shown to affect drug pharmacokinetics and pharmacodynamics, thereby influencing treatment response in terms of both efficacy and safety. These parameters must therefore be considered in pharmacological studies and clinical drug trials. From a precision-medicine perspective, clinical trials, preclinical and clinical research projects, and healthcare initiatives assessing sex- and gender-related differences that may influence health and disease status will also be included. In oncology, sex and gender affect cancer development and progression, as well as the efficacy and safety of anticancer treatments and adherence to diagnostic and therapeutic pathways. Although many sex-related differences have been described in oncology, women remain underrepresented in clinical trials. Their participation should therefore be increased, and potential sex- and gender-related differences should be appropriately investigated in routine clinical practice and in the development of clinical guidelines. The use of therapies increasingly tailored to the specific characteristics of the tumour, the patient’s clinical history, and the biological and sociocultural characteristics of each individual can improve efficacy, reduce treatment-related toxicity, and ensure that the most appropriate therapy is offered at each stage of the disease, thereby improving the quality of care. The implementation of new personalised and sex- and gender-sensitive therapeutic models will require technological investments, research aimed at improving omics-based molecular diagnostics, appropriate bioinformatics support, the implementation of multidisciplinary teams such as Molecular Tumour Boards, the expansion of network collaborations, and adequate resources for preclinical and clinical projects aimed at achieving a better understanding of sex- and gender-related differences.

Objectives

The general objectives of this research line are: - to strengthen and further develop molecular diagnostics and molecularly targeted cancer therapies, as well as the identification of genetic and epigenetic alterations predictive of response to targeted biological treatments, within a personalised-medicine framework; - to promote and support preclinical and clinical research on sex- and gender-related differences, so that the resulting knowledge and innovations can be translated into clinical practice and support the implementation of sex- and gender-sensitive medicine. Specific objectives: To implement technologies for molecular tumour profiling capable of identifying genetic and epigenetic alterations that may serve as molecular targets, through the use of gene panels of increasing complexity, RNA sequencing, whole-exome sequencing (WES), and whole-genome sequencing (WGS). To develop clinical and translational research projects aimed at monitoring the molecular evolution of tumours in both tissue and blood, thereby enabling the identification of resistance mechanisms. To develop standardised and reproducible methods for the biobanking of tumour tissue samples and biological fluids. To use the institutional Molecular Tumour Board to support advanced molecular investigations that can inform personalised therapeutic recommendations in clinical practice. To enrol patients in institutional and multicentre clinical trials evaluating innovative personalised therapies and specific patient subpopulations. To develop preclinical and clinical research projects investigating sex- and gender-related differences in oncology. To contribute to the development and extension of guidelines for sex- and gender-sensitive medicine in oncology.