Genetic Research – Dr Collet Dandara
Dr Collet Dandara
Title of the Project
Investigating expression of xenobiotic metabolising enzyme genes in human cancer cell lines
Highlights of the Project
Cancer cell lines at different stages of cancer progression exhibit different gene expression profiles of xenobiotic metabolising enzyme genes. The resultant effects (e.g. increased toxicity or proliferation) of potential carcinogens when applied to cancer cell lines are dependent on the genetic variants with respect to CYP1A1, CYP1A2 and CYP1B1. This point to the possibility that patient response to cancer drugs is modified by inherent genetic polymorphisms.
What has been achieved to date?
People are exposed to many carcinogens in everyday life. Some of the carcinogens cause the formation of cancer. However, each person inherits certain characteristics from their parents that either makes them have a higher or lower risk to develop cancer when exposed to the same amount of carcinogen as the second person. The same characteristics that make other people more at risk of developing the cancer also determine how these individuals respond to commonly administered chemotherapy. This study seeks to find out which of these characteristics one get from their parents make them respond in the way they do to either carcinogens resulting in development of cancer or chemotherapeutic drugs resulting in either favourable or adverse responses.
In order to understand which characteristics are important, we are starting this work in cancer cell lines (oesophageal, cervical and liver) which were derived from cancers at different tumour stages. We are treating (adding) chemicals (that we know humans are constantly exposed to) to these cell lines and investigating what is happening in terms of the inherited characteristics that are either supposed to protect us from getting cancer or helping to be able to benefit when we are being treated for cancer. We are observing that different chemicals (or drugs that are taken as therapy) need the presence of certain inherited characteristics (genes) for them to be removed from the cells or for the cell not to die. These findings are still preliminary and will be consolidated once our current analysis is finished.
At the end of the project, we are hoping to have discovered genes (inherited characteristics) respond to chemicals or carcinogens in such a way that their levels in the cells might suggest the possibility of early warning of cancer development. This will then enable early treatment (one of the problems with cancer is late diagnosis). We are also hoping we might discover genes which could be either blocked when one is taking certain chemotherapeutic drugs or genes which need to be induced in order to reduce most of the associated adverse drug effects.
How is the project of value in the struggle against cancer?
This project may result in the identification of crucial drug metabolism genes which are critical in the response to cancer treatment.
- Genetic research
- Inherited characteristics