The Research Unit (Chief: Massimo Serra) is focused on the identification of genetic and molecular bases responsible for the reduced sensitivity to chemotherapeutic drugs and associated with the development of adverse treatment-related toxicities in osteosarcoma.

Moreover, this Research Unit also studies the preclinical activity of new therapeutic approaches based on the use of drugs and compounds which are able to bypass or overcome the mechanisms of natural or acquired drug resistance or to enhance the activity of conventional chemotherapeutics within precise genetic contexts.

The most relevant investigation fields of the Research Unit are:

• Pharmacogenomic and pharmacogenetic characterization of osteosarcoma
• Analysis of genetic and molecular mechanisms responsible for resistance to doxorubicin, methotrexate and cisplatin, as well as of drugs used in rescue chemotherapy protocols, in human osteosarcoma cells
• Preclinical validation of candidate prognostic and therapeutic targets in high-grade osteosarcoma
• Preclinical assessment of the efficacy of new antitumour agents and of their interactions with conventional chemotherapeutic drugs.

The main research activities of the Research Unit are:

• Identification of biomarkers, which may be used for an early identification of patients with higher probability to develop clinical drug resistance and/or adverse treatment-related toxicities 
• Indication of new antitumoral agents, which may be considered for planning alternative and/or tailored treatment regimens for patients unresponsive or scarcely responsive to conventional chemotherapy.

Biologist Massimo Serra, together with MD Marco Gamabarotti, Head of the Laboratory of Pathology of the Rizzoli Orthopaedic Institute, is the Scientific Head for the analysis of ABCB1 expression in osteosarcoma patients, who have been enrolled in the Italian Sarcoma Group ISG/OS-2 treatment protocol (https://ClinicalTrials.gov/show/NCT01459484) and in the Grupo Español de Investigación en Sarcomas (GEIS) GEIS-33 trial. This activity, still active, involves different researchers of the research unit.

The Pharmacogenomics and Pharmacogenetics Research Unit hosts fellows and PhD students for training and preparation of experimental theses.

Ongoing research project:

Italian Ministery of Health 

• 2018-21: “Efficacy assessment of new targeted combination therapies for musculoskeletal sarcomas as the basis for tailoring patients' treatment”. Principal Investigator: Piero Picci. Co-Principal Investigator: Massimo Serra.

Italian Association for Cancer Research (A.I.R.C.)

• 2019-23: “Toward tailored treatments for osteosarcoma through validation of pharmacogenomic markers”. Principal Investigator: Massimo Serra.

European Community (ERA-NET/Transcan)

• 2019-22: "Harnessing BRCAness as therapeutic target in HR pediatric solid tumors (BRCAddict)". Principal Investigator for the Rizzoli Orthopaedic Institute: Massimo Serra. Co-Principal Investigator for the Rizzoli Orthopaedic Institute: Katia Scotlandi.

Completed research projects:

Italian Association for Cancer Research (A.I.R.C.)

• 1999-2000: "Molecular mechanisms of drug resistance in sarcomas". Principal Investigator: Massimo Serra
• 2002-03: "Study of genetic and molecular mechanisms of drug resistance in osteosarcoma as basis for innovative therapies". Principal Investigator: Massimo Serra
• 2003-06: "Profili genetici e biomolecolari di prognosi e predittività della risposta ai farmaci nei sarcomi muscoloscheletrici". Principal Investigator: Massimo Serra
• 2007-09: "Validation of candidate drug resistance-related genes in osteosarcoma". Principal Investigator: Massimo Serra
• 2010-13: "Overcoming drug resistance in osteosarcoma by targeting ABC transporters and protein kinases". Principal Investigator: Massimo Serra
• 2015-17: "Cisplatin resistance in osteosarcoma: Validation of new therapeutic targets and drugs for tailored clinical approaches". Principal Investigator: Massimo Serra.

Italian Ministry of Health

• 2003-05: "Biomolecular and genetic profiles associated with prognosis and predictive for drug responsivity in muscoloskeletal tumors". Principal Investigator: Massimo Serra
• 2007-11: “Development of new therapies for muscoloskeletal sarcomas: comparison between immunotherapy and target therapy”. Alliance agains Cancer – Program 3. Principal Investigator of the Rizzoli Orthopaedic Institute Unit “IOR-Serra”: Massimo Serra
• 2008-12: “Multidimensional characterization of solid tumors”. Programma Integrato Oncologia (Integrated Oncology Program - PIO 2006). Principal Investigator of the Operative Unit 6 “IOR”: Massimo Serra.

European Community

• 2006-11: “European Network of Excellence to Promote Research into Uncommon Cancers in Adults and Children: Pathology, Biology and Genetics of Bone Tumours (EuroBoNeT)”; work package “Drug response and pharmacogenomics in osteosarcoma”; Principal Investigator: Massimo Serra
• 2006-10: Scientific Head of the Research Program funded by the European Community “Selecting and validating drug targets from the human kinome for high risk paediatric cancers (KidsCancerKinome, KCK)” (6th Framework Programme for Research and development FP6-2005-LIFESCIHEALTH-6037390) for the Rizzoli Orthopaedic Institute. Principal Investigator IOR: Massimo Serra.