Istituto Mario Negri

Head

Maurizio

D'Incalci

Head Department

Oncologia

maurizio.dincalci@marionegri.it

Staff

Maura

Montani

Assistant

Oncologia

maura.montani@marionegri.it

The goal of the Department of Oncology is to offer therapies for the treatment of tumors more effective through studies that investigate molecular, biological and pharmacological aspects.

The final goal is to obtain clinical applications which could ameliorate survival and quality of life of oncological patients.

The projects carried out by the Department concern different types of tumors, but the majority of preclinical and clinical studies focus on gynecological tumors, sarcomas, thoracic tumors (lung, mesotheliomasand thymomas) and pancreatic tumors.

ObJECTIVES

Identify new "druggable" molecular targets and also biomarkers which should be diagnostic, prognostic and predictive of responsiveness to specific cancer therapies
Study of tumors biology, and in particular of their growth, neoangiogenesis, metastasization and interaction with immunological mechanisms
Study of the mechanism of action and of the pharmacokinetic and pharmacodynamic properties of new anticancer drugs, characterized by an innovative mechanism of action able of acting directly on the tumor or on its interaction with the host
Study of anticancer drugs resistance and of the possible methods to elude it
Study of new combinations of drugs and of their "off-label" use, both in experimental models and in the clinic

METHODOLOGICAL APPROACHES

Use of material from biobanks that allows the implementation of retrospective studies. The Department of Oncology owns an ovarian carcinomas biobank, collecting neoplastic tissues and biological fluids deriving from more than 3000 cases, also accompanied by an average updated 10-year clinical follow-up. The biobank or Biological Resource Center (CRB) is certified UNI EN ISO 9001: 2015 (No. 6121) from 2014 for the following activity: "Collection, conservation and distribution of biological samples and related data for scientific research studies"
Use of in vitro and in vivo experimental models directly derived from human samples, of ovarian tumors obtained from surgical biopsies of patients affected by this tumor as well as of sarcomas or human mesotheliomas. These models called PDX, Patient Derived Xenograft, have been developed and characterized in department laboratories from the biological, pathological and pharmacological point of view.
Development of genetic models, which reproduce important molecular alterations, to study the biology of different human tumors and the sensitivity to specific classes of drugs
Development of human tumor models in mice, in which the tumor was chemically induced (for example sarcomas or mesotheliomas induced by carcinogens) or through genetic manipulations
Development, validation and use of highly specific and sensitive methods for the quantitative measurement of drugs and of their metabolites in normal or neoplastic tissues. Among methods used, first HPLC-MS/MS for preclinical and clinical pharmacokinetic studies and also for spatial drugs visualization, and, last but not the least, the new generation Imaging Mass Spectrometry technique
Use of NGS, Next Generation Sequencing, techniques for genomic, transcriptomic and proteomic studies, correlated by a bioinformatic competence
Planning, Management, Conduction, Monitoring and Analysis of data deriving from phase I, II and III clinical studies through state-of-the-art and pharmacovigilance statistical approaches

Results

Improved survival of patients affected by myxoid liposarcoma, a very rare sarcoma, thanks to the development of a new drug coming from the sea, trabectedin
Development of new preclinical murine experimental models of thymomas and mesotheliomas to identify new and more effective therapies
Development of a new imaging methodology which allows to test the ability of anticancer drugs to penetrate, homogeneously, into different tumor layers, improving the efficacy of the therapy

Current projects

‍Development of new therapies for tumors that metastatize the bone

Sponsor: Fondazione Beppe e Nuccy Angiolini

Research area: Bone tumors

A multicenter phase III randomised study with second-line chemotherapy plus or minus bevacizumab in patients with platinum-sensitive epithelial ovarian cancer recurrence after a bevacizumab/chemotherapy first line

Sponsor: Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"

Reasearch area: Ovarian tumors

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ERANET - Euronanomed III JTC - 2018 - CONCORD - Cationic Gold nanoparticles mediated mRNA cytoplasmatictargeted delivery for production of CAR-T lymphocytes for Chronic Lymphoid Leukemia immunotherapy

Sponsor: Ministero della Salute, DG Ricerca e Innovazione in Sanità

Reasearch area: Leukemia, nanoparticles

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Ricerca Finalizzata - GR-2016-02361849 - Liquid biopsies as predictors of response in advanced Non-Small Cell Lung Cancer patients receiving immune checkpoint inhibitors

Sponsor: Ministero della Salute, DG Ricerca e Innovazione in Sanità

Reasearch area: Lung cancer

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Improving treatment strategies in thymic epithelial tumors: a TYME collaborative effort

Sponsor: Agenzia Italiana del Farmaco AIFA

Research area: Timomas

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EXemestane in Progesterone and/or Estrogen receptor positive epithelial ovarian cancer. A Randomized phase III Trial, EXPERT

Sponsor: Agenzia Italiana del Farmaco AIFA

Research area: Ovarian cancer

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Open-label, randomized controlled trial comparing tocilizumab to anti-TNF treatment and discovery of biomarkers for treatment selection in rheumatoid arthritis patients with inadequate response to a first anti-TNF (RAFTING)

Sponsor: Agenzia Italiana del Farmaco AIFA

Research area: Rheumatoid arthritis

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Exploiting LKB1 vulnerability by selective metabolic treatments in advanced Non-Small Cell Lung Cancer