Radiobiology applied to Oncology
Major assets in Radiobiology
Benefiting from the installation of an advanced radiotherapy technology park and a laboratory for radiobiology research on the same campus, this Program aims to develop original and competitive translational research in the field of oncologic radiotherapy.
The implementation of this Program relies on an already well-structured network, the close relationship between the ICM and the IRCM having fostered close links between clinicians and researchers working on this theme.
The Coordination of this Program is provided by a clinician and a researcher working together; Pr David Azria, Coordinator of the Oncology radiotherapy Division of the ICM, and Dr. André Pelegrin, Director of the IRCM and Team Leader of ‘Immuno-targeting and Radiobiology in Oncology’.
This collaboration allows for the combining of major clinical and scientific advances in the field of anti-tumour therapies via antibodies and their association with ionising radiations.
New strategies for personalised radiotherapy
Effective external radiation therapy requires the homogeneous delivery of an adequate total dose to the targeted tumor tissue. In addition and in many tumor indications, combined treatment of ionizing radiation and drugs has proven its superiority compared to radiation alone in terms of locoregional control. Dose delivery with or without systemic molecules may however be hindered by the tolerance of surrounding normal tissues in the irradiated volume. While the potential side effects of radiation therapy are numerous and well-described, it is currently impossible to predict the extent of such effects for a given individual patient. This was one of the bases of development of predictive assays to identify patients harboring an intrinsically greater risk to develop severe late normal-tissue toxicity in the era of combined external radiation and medical strategies.
The goal of this program is to improve knowledge of radiobiological parameters predictive of efficiency and tolerance to ionizing radiation in order to develop new strategies in personalised radiotherapy. Strategic directions for the program are focussed on two main objectives:
WP1 – Optimising targeted therapies combining radiotherapy and innovative drugs
This first area of research aims to study the therapeutic effect of radiotherapy combined with new targeted therapies.
For patients necessitating a local irradiation in a curative intent, the antitumor effect depends on the total dose delivered to the target volume and/or the synergism of radiotherapy and radiosensitizers within the tumor fields.
In this context, we have started projects aiming (i) to increase the total dose in a limited volume and (ii) to combine targeted drugs with ionizing radiation. The purpose is to investigate the action mechanisms induced by the association of therapeutic antibodies (anti_EGFR, HER2, HER3) with ionising radiation in order to improve the radiosensitivity of the tumour cells. These associations are studied both in vitro and in vivo in different pre-clinical models of cancer such as cancer of the breast, the pancreas, the rectum, the anal canal, cervical cancer and cancer of the upper aero-digestive tract.
WP2 – Characterising predictive determinants of radiation-induced late side-effects after curative intent radiotherapy
In collaboration with Pr Ozsahin (CHUV, Lausanne), we started the “predictive assay” translational program to identify patients at risk of developing side-effects. It was clear that a rapid, reproducible test based on lymphocyte response would be of value in radiotherapy. We have developed a blood test allowing the identification of patients at risk of developing late side effects after curative-intent radiotherapy. This test is based on the analysis of the radiosensitivity of the blood lymphocytes.
A high level of lymphocyte apoptosis is correlated to a close to zero risk of developing late effects after curative radiotherapy (negative predictive value around 99%).
These studies have led to the identification of radio-induced lymphocyte proteins able to discriminate patients hypersensitive to therapeutic radiation from patients having developed no late secondary effects. The current objective is to evaluate the role of these proteins in the establishment of late radio-induced toxicity and to understand the molecular and cellular processes present in these patients.