Investigating biochemical signatures of radiation resistance in human breast and prostate cancers via single cell Raman spectroscopy

Radiation therapy is the recommended treatment for about one-third of all cancer patients, including those with breast and prostate cancer. One factor limiting the use of radiation therapy is the considerable difference in radiation response between patients. There are currently no proven biochemical or imaging methods to assess a cancer patient's radiation response during an extended radiation therapy treatment. There is a need to develop customized radiation treatments to accommodate the variations in radiation response from individual patients; however, implementing such personalized treatments requires a better understanding of the fundamental biochemical responses of human tumour cells to ionizing radiation. Dr. Quinn Matthews is investigating the use of Raman spectroscopy as a way to monitor radiation responses in cancer patients undergoing radiotherapy. Raman spectroscopy is a non-invasive technique that shows great promise for the biochemical analysis of cellular radiation responses, as it can provide sensitive molecular information from biological samples, such as human cells or tissues. Recent laboratory studies have shown that single-cell Raman spectroscopy techniques applied to irradiated cells can detect radiation-induced changes in certain proteins, lipids and nucleic acids within human prostate, breast and lung tumour cells. These results suggest that certain types of radiation-induced biochemical changes measured with Raman spectroscopy are correlated with tumour-cell resistance to radiation treatment. The goal of Dr. Matthews' research project is to apply the proven capabilities of Raman spectroscopy to investigate the biochemical radiation response of a variety of human breast and prostate cancers, irradiated both in vitro (in the lab) and in vivo (in the organism). The results of this research will lead to increased effectiveness of radiation therapy by facilitating the development of personalized adaptive treatments designed to account for individual radiation response.

Mechanical stress: an unexplored factor in regulation of cell signaling in DCIS and early breast cancer progression

Breast cancer is the second most common cause of cancer-related deaths among women in Canada. Deaths caused by invasive breast cancer that metastasizes (spreads to other parts of the body) are mostly preceded by a pre-invasive stage of the disease called ductal carcinoma in-situ (DCIS). This early stage is the ideal target in prevention of invasive breast cancer. Research has confirmed that features of the molecular activity of normal wound healing may play an important role in the spread of cancer from one area of the body to another. As cancer develops within any organ there is disruption of normal tissue. This disruption is like a wound and the response is like a scar. This process results in new mechanical forces within the tissue that act like a stress on tumor cells and have the potential to strongly influence a large number of cellular processes associated with tumor growth and invasion. Dr. Jiaxu Wang is researching the role of mechanical stress on cancer cells. He is investigating which genes are altered by mechanical stress in breast cancer cells. Wang is also identifying genes that are specifically altered by mechanical stress but not by other forms of stress that are known to exist in cancer tissues, such as lack of oxygen, to determine if these genes can be used to measure mechanical stress in DCIS lesions. The research will contribute to a better understanding of the specific role of mechanical stress in breast cancer progression. Wang’s ultimate goal is to develop markers that can predict or provide targets for therapy to improve outcomes for women with pre-invasive and early breast cancer.

PREDICT: Personalized Response Determinants in Cancer Therapy

This award supports the development of an interdisciplinary team that embeds research into front line cancer care. The goal is to develop a blood and DNA bank from consenting patients with newly diagnosed cancer, to serve as a resource for studying the causes of cancer as well as responses to, and outcome of, cancer therapies.