Descrizione del progetto
Progredire nella comprensione e nel trattamento del tumore polmonare a piccole cellule
Il tumore polmonare a piccole cellule è un tipo aggressivo di tumore polmonare con un’elevata propensione metastatica. Il trattamento è rimasto uniforme per decenni e di solito prevede la chemioterapia e la radioterapia, senza progressi significativi. Il progetto BIOSMALL, finanziato dal programma di azioni Marie Skłodowska-Curie si basa sull’ipotesi che il trattamento del tumore polmonare a piccole cellule debba differenziarsi in base alle caratteristiche molecolari e cliniche dei pazienti. I ricercatori utilizzeranno tecnologie multiomiche per correlare i profili molecolari con il comportamento metastatico e la risposta al trattamento con potenziali farmaci mirati. L’analisi genetica e l’apprendimento automatico contribuiranno ulteriormente a identificare le caratteristiche dei sottotipi, aprendo la strada a strategie diagnostiche e terapeutiche complete per il tumore polmonare a piccole cellule.
Obiettivo
Although small cell lung cancer (SCLC) is a particularly aggressive disease, targeted therapies have remained largely unsuccessful and there were no major therapeutic advances in the last three decades. In the clinics, SCLC is still treated as a molecularly homogeneous malignancy. However, recent analyses led to the classification of neuroendocrine and molecular subtypes, defined by differential expression of four key transcription regulators: ASCL1, NEUROD1, POU2F3 and YAP1. Our study proposal aims to identify unique subtype-specific diagnostic and therapeutic biomarkers for SCLC patients with state-of-the-art multiomic approaches, and moreover to deepen our understanding of the biological and clinical significance of SCLC molecular subtypes. We intend to investigate the diagnostic and therapeutic significance of each subtype in a large panel of human SCLC cell lines in correlation with their proteomic and metabolomic profiles, in vivo metastatic capacity and sensitivity to potential targeted agents. Additionally, the specific features of the molecular subtypes will be also assessed by performing genetic mutation analyses and using in-depth machine-learning algorithms. All potential circulating biomarkers delineated by proteomics and metabolomics will be first validated by a series of in vivo experiments in different murine models. In addition, in order to improve patient selection and follow-up in a non-invasive manner, the specific PET-CT radiomic features of enrolled patients will be also analysed within the framework of the current study. Altogether, by identifying a wide range of novel biomarkers and potential therapeutic targets via multiomic approaches, the current study will possibly result in a new subtype-specific biomarker panel which will contribute to the development of individualized diagnostic and/or therapeutic strategies in this hard-to-treat disease.
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Meccanismo di finanziamento
HORIZON-TMA-MSCA-SE - HORIZON TMA MSCA Staff ExchangesCoordinatore
1090 Wien
Austria