Radiation is one of the primary modalities for the treatment of localized cancer and a number of factors can influence the response of tumours and surrounding normal tissues to such treatment. These factors, which can be specific to the individual tumour or normal tissue and to their environment, can vary from patient to patient. One part of the research in my laboratory focuses on understanding how these factors control tumour and normal tissue response to radiation treatment in individual patients.Our current work involves:
- Examination of hypoxia in human tumours with a focus on cancer of the cervix and soft tissue sarcomaIn these studies we are collaborating with the clinical groups at the Princess Margaret Hospital in examining methods to measure hypoxia in tumours in relation to their value as predictors of treatment outcome.
- Studies of the cellular radiosensitivity of normal human fibroblasts from skin in vivoThese studies are focusing on the use of assays of fibroblast response to irradiation as a possible local dosimeter following accidental exposure to irradiation.
- Examination of the sensitivity of lung tissue to different volumes of irradiationThese studies in rat and mouse lungs are investigating mechanisms associated with the response of the lung to radiation damage (believed to be associated with the induction of a localized but prolonged inflammatory response), which can result in deleterious effects both inside and outside the radiation field.
The second major focus of our research is the spread of cancer from its initial site of growth to other locations in the body (metastasis), which is a major factor influencing the likelihood of successful treatment. The formation of metastasis by tumour cells is thought to be dependent on the expression of specific phenotypes by individual tumour cells. Our research is examining metastatic phenotypes that are expressed only transiently and that may be induced by exposure of tumour cells to conditions, such as hypoxia, which occur in the tumour microenvironment. Recent clinical results have suggested that tumours that contain substantial hypoxic regions may be more likely to form metastases. We have found in animal model systems that exposure to hypoxia, both in vitro and in vivo, can cause transient increases in the metastatic potential of tumour cells and that exposure to transient hypoxic episodes may be particularly important for this increased metastatic potential. We are examining the effect of hypoxic exposure in modifying the expression of genes likely to be associated with the cancer stem cell phenotype, metastasis and tumour progression. Recent studies by our clinical collaborators have identified elevated levels of interstitial fluid pressure, a characteristic of many tumours, as another factor that may affect metastasis. We are developing animal models to investigate the mechanisms responsible for this effect.
Clin Transl Radiat Oncol. 2019 Nov;19:110-115
Correction: Targeting CXCL12/CXCR4 and myeloid cells to improve the therapeutic ratio in patient-derived cervical cancer models treated with radio-chemotherapy.
Br J Cancer. 2019 Aug 09;:
Targeting CXCL12/CXCR4 and myeloid cells to improve the therapeutic ratio in patient-derived cervical cancer models treated with radio-chemotherapy.
Br J Cancer. 2019 Jul;121(3):249-256
Radiat Res. 2019 Apr;191(4):380-381
Int J Radiat Biol. 2019 Mar 05;:1-2
Understanding Real-Time Fluorescence Signals from Bacteria and Wound Tissues Observed with the MolecuLight i:XTM.
Diagnostics (Basel). 2019 Feb 26;9(1):
ERβ agonist alters RNA splicing factor expression and has a longer window of antidepressant effectiveness than estradiol after long-term ovariectomy
J Psychiatry Neurosci. 2019 Jan 01;44(1):19
Using Bacterial Fluorescence Imaging and Antimicrobial Stewardship to Guide Wound Management Practices: A Case Series.
Ostomy Wound Manage. 2018 Aug;64(8):18-28
ERβ agonist alters RNA splicing factor expression and has a longer window of antidepressant effectiveness than estradiol after long-term ovariectomy.
J Psychiatry Neurosci. 2018 Aug 14;43(5):170199
The predictive value of nadir neutrophil count during treatment of cervical cancer: Interactions with tumor hypoxia and interstitial fluid pressure (IFP).
Clin Transl Radiat Oncol. 2017 Oct;6:15-20
Emeritus Scientist, Princess Margaret Cancer Centre
Professor, Department of Radiation Oncology, University of Toronto
Professor, Department of Medical Biophysics, University of Toronto