Over the last two decades Simone Mocellin has been actively involved in the following main research fields: 1) predictive and prognostic biomarkers for setting up predictive and prognostic models leading to the clinical implementation of nomograms for better patient selection and risk stratification (with special regard to cutaneous melanoma and soft tissue sarcomas); 2) the role of sentinel node biopsy and radical lymphadenectomy in the therapeutic management of patients with solid tumors (with special regard to melanoma, gastrointestinal cancer and breast cancer); 3) the role of cytoreductive surgery and locoregional treatments in the therapeutic management of patients with solid tumors (with special regard to in transit melanoma metastases, limb-threatening soft tissue sarcomas, retroperitoneal soft tissue sarcomas, peritoneal carcinomatosis and sarcomatosis, unresectable liver metastases); 4) systematic reviews and meta-analyses (in the field of cancer risk epidemiology and molecular epidemiology, diagnosis, prognosis, therapy, network meta-analysis, dose-response meta-analysis) to support guidelines of evidence based medicine.
Director of the Soft tissue, Peritoneum and Melanoma Surgical Oncology Unit
– Surgical Oncology Department, IOV-IRCCS
– Full Professor of Surgery, Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy
Research activity
PD1 AND PDL1 EXPRESSION AS THERAPEUTIC TARGETS AND PROGNOSTIC BIOMARKERS IN SOFT TISSUE SARCOMAS
PD1 and PDL1 are key regulators of the adaptive immune reponse and might be novel therapeutic targets and prognostic markers for patients with soft tissue sarcomas.
Research topic
New therapeutic targets and prognostic biomarkers for soft tissue sarcomas.
Background
PD1 and PDL1 (which belong to the immune checkpoint family of receptors/ligands) are being currently used in the clinical practice as terapeutic targets for different tumor types (e.g., melanoma, lung cancer, renal cell carcinoma and so on), but they have not been investigated in soft tissue sarcomas. Moreover, no data are available on their role as prognostic biomarkers. We intend to assess whether or not PD1 and PDL1 are expressed (and to what degree) in a range of soft tissue sarcoma types so to provide the rational for their use as terapeutic targets and or prognostic markers. Therefore, this study has a typical translational design as it aims to identify patients responsive to immune checkpoint inhibitors and to select patients suitable for adjuvant treatments, according to the principles of personalized medicine.
Research achievements
We have collected in our biobank tumor specimens from more than 500 patients affected with soft tissue sarcomas. The clinical data of these patients are being gathered as well. The expression of PD1 and PDL1 (by immunohistochemistry) has been planned to be assessed by means of image analysis technology.
Perspectives
Should we find that soft tissue sarcomas (or some histological subtypes) express PD1 and or PDL1, our results could represent the rational for carrying out clinical trials on the use of already existing anti-PD1 or anti-PDL1 blocking antibodies for the treatment of soft tissue sarcomas. Moreover, if the expression of PD1 and or PDL1 had an independent prognostic role, it could be implemented in the clinical setting to stratify the risk of disease recurrence and thus to select patients who most need adjuvant treatments after apparently radical surgery (adjuvant therapy).
Team members
CLOCK GENES POLYMORPHISMS AS RISK AND PROGNOSTIC FACTORS IN MELANOMA AND SOFT TISSUE SARCOMAS
New risk and prognostic factors are needed to improve our ability to select individuals to be screened and to select patients who most need adjuvant therapy.
Research topic
New risk and prognostic factors for melanoma and soft tissue sarcomas.
Background
Disregulation of the biological clock (through altered activity of the protein products of so called clock genes) has been recently linked to the carcinogenesis of tumor types (mainly breast cancer), but they have not been investigated in melanoma and soft tissue sarcomas. Moreover, no data are available on their role as prognostic biomarkers. We intend to assess whether or not germ-line variation of a set of clock genes can play a role in the predisposition and prognosis of melanoma and soft tissue sarcomas. Therefore, this study has a typical translational design as it aims to identify individuals who should be enrolled in screening programs and to select patients suitable for adjuvant treatments, according to the principles of personalized medicine.
Research activities
We have collected in our biobank the peripheral blood from more than 600 patients affected with melanoma or soft tissue sarcomas as well as 400 healthy individuals. The clinical data of these patients are being gathered as well. Gene variation has been planned to be assessed by means of quantitative real time PCR.
Perspectives
The results of this study might lead to the identification of new risk biomarkers for cutaneous melanoma and soft tissue sarcomas. This would ultimately allow to identify individuals at high risk of developing these tumors, and thus suitable for intensified screening. Moreover, if the investigated polymorphisms had an independent prognostic role, they could be implemented in the clinical setting to stratify the risk of disease recurrence and thus to select patients who most need adjuvant treatments after apparently radical surgery (adjuvant therapy).
Team members
- Clara Benna
- Saveria Tropea
- Antonella Vecchiato
- Marco Rastrelli
- Paolo del Fiore
- Romina Spina
Selected references
- Rastrelli M, Mocellin S, Stramare R, Brunello A, Maruzzo M, Basso U, Scarzello G, Buzzaccarini MS, Pilati P, Saadeh LM, Del Fiore SP, Tosi A, Montesco C, Campana LG, Tropea S, Rossi CR. Isolated limb perfusion for the management limb threatening soft tissue sarcomas: The role of histological type on clinical outcomes. Eur J Surg Oncol. 2017 Feb;43(2):401-406
- Rossi CR, Mocellin S, Campana LG, Borgognoni L, Sestini S, Giudice G, Caracò C, Cordova A, Solari N, Piazzalunga D, Carcoforo P, Quaglino P, Caliendo V, Ribero S; Italian Melanoma Intergroup (IMI). Prediction of Non-sentinel Node Status in Patients with Melanoma and Positive Sentinel Node Biopsy: An Italian Melanoma Intergroup (IMI) Study. Ann Surg Oncol. 2018 Jan;25(1):271-279
- Mocellin S, Tropea S, Benna C, Rossi CR. Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies. BMC Med. 2018 Feb 19;16(1):20