Luigi Corti is Head of the Radiotherapy Unit since 2014 and has a longstanding experience as Radiation Oncologist. The research activity concerns the assessment of impact and efficiency of different radiotherapy procedures, as testified by the personal record of publications from early 1980s. Recently, he has started a collaborative project involving a staff with different expertise (clinical oncology and radiotherapy, molecular and cellular biology, genetics, radiobiology), with the goal to set up and validate predictive biomarkers of radiosensitivity/radioresistance and to correlate them with clinical radiation-induced toxicity. This information should provide the basis to define individualized radiotherapy protocols.

Radiotherapy Unit
Department of Radiological Sciences and Medical Physics

Research activity

Identification of new biomarkers of radiosensitivity/resistance for patient stratification and personalized radiotherapy treatment planning

Our aim is to define a genetic signature to be integrated with clinical scores of radiation-induced toxicity for the prediction of individual response of cancer patients to radiotherapy.

Research topic

The personalization of radiotherapy (RT) represents the goal of future clinical radiation trials. A screening tool able to classify each patient according to his/her own sensitivity to ionizing radiation (IR) before the administration of RT would be essential to set personalized dosing schedules, effective in improving RT outcomes and in reducing side effects.

Background

During radiotherapy (RT) normal tissue is unavoidably exposed to radiation (IR) resulting in severe normal tissue reactions in a small fraction of patients. Because radiosensitive patients cannot be identified prior to RT, the doses are limited to all patients to avoid an unacceptable number of severe adverse normal tissue responses. This limitation restricts the optimal treatment for individuals who are more tolerant to IR. Genetic variation is a likely source for the normal tissue radiosensitivity variation observed among individuals. Mutations in key genes of the DNA Damage Response (DDR) pathway, or the individual modulation of DDR gene expression after IR-exposure, may underlie these differences.

Research achievements

Our goals are the following: 1) definition of individual gene expression profiles on blood samples of patients undergoing RT; 2) evaluation of the correlation between the individual radiosensitivity values (IRS) based on G2-assay, and the clinical symptoms reported by the patients; 3) validation of the radiosensitivity tool for patient stratification for less risk of short- and long-term side effects. At present, IRS values are available for almost 80 patients; expression data concerning a set of 4 genes of the DDR pathway were obtained for about 20 patients. The preliminary results confirm the feasibility of our approach.

Conclusions and perspectives

This study aims at defining a genetic signature useful to discriminate patients undergoing RT as radiosensitive, normal and radioresistant and to predict the likelihood of a late IR-toxicity. In this frame, gene expression data concerning DDR pathway, obtained from blood samples of breast and head-neck cancer patients, are overlaid with the individual in vitro radiosensitivity index and the in vivo tissue radiosensitivity detected during the follow-up. The innovation of this project is the use of a molecular biology approach to assess patients’ radiosensitivity before RT, in the frame of an integrated approach between clinicians and biologists.

Team members

  • Lucio Loreggian
  • Elena Groff
  • Elena Fasanaro
  • Fabio Busato
  • Michele Rigo
  • Badr El Khouzai
  • Roberto Di Carlo
  • Laura Baggio
  • Elisa Palumbo
  • Celeste Piotto

Italian Institut of Nuclear Physics 

  • Demetre Zafiropoulos

University of Padova

  • Antonella Russo
  • Maddalena Mognato
  • Chiara Romualdi
  • Enrica Calura

Selected references