Mercoledì 27 Settembre 2023
ore 13 Edificio Asclepio U8 - Aula 2
Host Dott. Daniele Ramazzotti
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Cancers evolve obeying Darwinian laws and therefore the evolutionary paradigm lays the ground for predictive oncology. However, the predictive power of evolutionary metrics in cancer has seldom been tested. There is a need for quantitative measurements in controlled clinical trials with long term follow-up information. Here we mapped genomic intra-tumour heterogeneity using 642 tumour samples from 114 patients who took part in prostate radiotherapy trials at The Royal Marsden Hospital, for which full clinical information and 12y median follow-up was available. We concomitantly assessed phenotypic (morphological) heterogeneity using Deep Learning in 1,923 histological sections from 250 IMRT patients. We found that evolvability, measured as genetic divergence as well as morphological (Gleason) diversity, were strong independent predictors of recurrence. Combined, these two measurements identified a group of patients with half the median time to recurrence compared to the rest of the cohort (5.6 vs 11.5 years). Spatial genetic segregation of clones was also an independent marker of recurrence. Matched genomic profiling of the tumour at recurrence, up to 20 years after primary diagnosis, confirmed the role of genomic instability as a driving force in prostate cancer progression. This study shows that combining genomics with AI-aided histopathology in clinical trials leads to the identification of novel clinical biomarkers.
Prof. Andrea Sottoriva - Computational Biology Research Centre, Human Technopole
Andrea Sottoriva is the Head of the Computational Biology Research Centre at Human Technopole.
Andrea’s research focuses on the development of new computational approaches to measure cancer evolution in patients, with the aim of predicting the future course of the disease. Andrea’s lab also integrates patient-derived experimental models and multiomics data, with evolutionary methods to design new treatment strategies that aim at preventing and controlling drug resistance.
After graduating in Computer Science at the University of Bologna in 2006, he obtained a master in Computational Sciences from the University of Amsterdam in 2008. During his studies, he worked in neutrino physics at the Department of Physics of the University of Bologna and at the Institute for Nuclear and High Energy Physics (NIKHEF) in the Netherlands as a research assistant.
In 2012 he completed his PhD in Computational Biology from the University of Cambridge, where he worked at the Cancer Research UK research centre.
After postdoctoral work at the University of Southern California, he started his lab at the Institute of Cancer Research in London in 2013, where in 2018 he became the Deputy Director of the Centre for Evolution and Cancer and then the Director in 2020.