PRESENTAZIONE DI RUGGERO DE MARIA

Transcription

1 Iniziativa realizzata con il contributo di Pfizer Roma, 17 ottobre 2018 Sala Zuccari, Palazzo Giustiniani PRESENTAZIONE DI RUGGERO DE MARIA

2 La ricerca oncologica e le prospettive per il sistema Prof. Ruggero De Maria Presidente, Alleanza Contro il Cancro

3 Founders Ordinary Members IRE-Rome INT-Milan IDI-Rome Fond. Besta Milan Humanitas Milan IEO Milan San Raffaele Milan IOR- Bologna Fond. Pascale-Naples Fond. CSS-S. Giovanni Rotondo, FG Arcispedale S. Maria Nuova-RE IST San Martino-Genua IRCC - Candiolo, TO CRO-Aviano Giovanni Paolo II Bari F. Maugeri Milan New Members CROB-Rionero In Vulture (PT) ISS-Rome IOV Padua Gaslini Genoa IRST-Meldola SDN-Naples OPBG -Rome Adherent Associates Fond. Mondino-Pavia IRCCS S. de Bellis Bari Policlinico Gemelli Rome

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5 IST S. Martino IRST Meldola Gaslini IOR INT Reggio Emilia IEO ISS Humanitas IDI HSR OPBG Besta IRE Maugeri Pascale CRO CROB IRCC Candiolo INT Bari S. De Bellis S. Giovanni Rotondo IOV ACC Working Groups Lung Breast Colon Brain Melanoma Sarcoma Immuno therapy

6 Breast Cancer in Italy Every year 52,000 new cases of breast cancer are diagnosed in Italy Breast cancer accounts for about 42% of the total cost of cancer drugs in Italy ACC is acting on three major areas to fight breast cancer Improve prevention Avoid overtreatment Personalize therapies 1. Breast checks 2. Healthy weight 3. Active lifestyle 4. No smoke 5. No alcohol

7 Overall survival (%) Breast cancer: a heterogeneous disease Breast cancers have different: molecular profiles clinical features outcome Currently used markers: Hormone (Estrogen and Progesterone) Receptors HER2 Ki Weigelt, The Lancet Oncology, 11:339, 2010

8 Transcriptomic analysis for molecular stratification of breast cancer Multigene expression assays have a clinically validated prognostic utility in ER + HER2 - early-stage breast carcinoma (new ASCO guidelines exclude ki67 to distinguish luminal A from B) In this setting, their application could spare adjuvant chemotherapy in approximately 25% of patients. 21 genes 12 genes 70 genes 50 genes These tests are expensive (up to 3,000 ) and provide poorly concordant stratification when applied to the same patient. Thus we are developing a low-cost (300 ) high-performing RNAseq platform

9 Bringing RNA-seq to the clinic Global RNA-seq analysis measures all expressed genes RNA-seq has reasonable costs (below 400 ), that are expected to further decrease. Advantages of applying global RNA-seq profiling instead of a multigene classifier to clinical samples: RNA-seq allows concomitant stratification of the sample by multiple classifiers, for more robust prognostic/predictive analysis While providing clinically informative results, RNA-seq also allows developing novel multigene signatures and classifiers

10 Oncologists per 1 million population Availability of oncology drugs launched after 2012 Number of pipeline drugs in USA Trials with stratification biomarkers (number & percentage) (1,120 in clinical trials) DRUGS IN DEVELOPMENT Cancer type 1,120 Breast 160 Colorectal 105 Lung 153 Leukemia 151 Skin 108 Source: GlobalData, Pharma Intelligence Center, Drug Database

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12 Newly approved cancer drugs show limited benefit on survival or quality of life, both in clinical trial and particularly in real life!

13 Towards Precision Medicine

14 The ACC-Gersom Strategy Cancer Patient Gersom Genomic profile of every patient (tumor+germline) Detection of actionable somatic mutations MSI status Mutational burden Detection of germline pharmacogenomic variants Detection of driver-gene mutations Treatmentstratification Drug-toxicity New stratification markers Identification of germline variants for cancer risk: 172 genes Mapping of each risk-variant In family members Cancer prevention plans Registry of Somatic cancer-mutations Registry of Germline cancer-risk variants

15 Clinical Value of the Germline Actionable-Genome Genes Percent with Mutation Any deleterious mutation* Genes related to breast cancer* BRCA1 or BRCA2 6.1 BRCA1* 3.7 BRCA2* 2.5 Other genes related to breast cancer* 4.1 ATM* 0.8 BRIP1 0.8 CHEK2* 2.1 NBN 0.2 PALB2 0.2 PTEN 0.2 Genes not clearly related to breast cancer* 0.8 MSH6 0.2 PMS2* 0.2 RAD51C 0.2 RAD51D 0.2

16 I programmi di ACC per il cancro della mammella Migliorare la prevenzione Identificare le persone con predisposizione genetica ai tumori Evitare terapie inutili o dannose Sviluppare una piattaforma di RNAseq in grado di identificare le pazienti che non necessitano di chemioterapia adiuvante Usare la trascrittomica e la genomica per identificare preventivamente le pazienti che non rispondano alle terapie neoadiuvanti Screenare i polimorfismi dei geni coinvolti nel metabolismo dei farmaci per evitare le tossicità da accumulo Utilizzare terapie antitumorali più efficaci Evidenziare le alterazioni actionable per somministrare i farmaci potenzialmente più attivi Utilizzare i profili genomici e trascrittomici per stratificare le pazienti

17 Genomic database The ACC Prescription Database: Goals Create large-scale data resources of genomic information: Mutational Database Actionability infos Link the genomic database to: to EMRs and Health-System databases to research pipelines Interface with Doctors Create widely accepted and controlled vocabularies (ontologies) for clinical phenotypes Generate standards and pipelines for data interpretation and clinical decision support (automated decision support tools for clinicians) Interface with Patients Train patients in using genomic information Give patients access to the latest experimental protocols and drugs

18 Towards Precision Medicine Multi-Modality Data Integration is required for Precision Medicine

19 Digital Avatar for Precision Medicine Big Data & AI drive Precision Medicine Reducing Healthcare Costs & Improving the Management of Patients

20 Thank you!