Research Projects

Oesophageal cancer research – Dr Demetra Mavri-Damelin

Oesophageal cancer research – Dr Demetra Mavri-Damelin

Dr Demetra Mavri Damelin

Dr Demetra Mavri-Damelin

Project Title

Metformin treated oesophageal squamous cell carcinoma cells exhibit altered sensitivity to cisplatin.

Project Description

A tumour is made up of cancer cells but these cancer cells are not all identical, for example some cells grow faster or may require more energy and oxygen to grow than others. As such, treating cancer is made very difficult as not all cancer cells will respond in the same way to a specific type of treatment.  This can lead to drug resistance, which is highly problematic for the successful treatment of cancer. One of the options to combating resistance is to combine different chemotherapeutic drugs that can destroy different types of cells at the same time.  This research aims to identify new treatment combinations for individuals with oesophageal squamous cell carcinoma (OSCC), one of the most common cancers affecting South Africans.

Non-scientific report

Poor response and resistance to chemotherapeutic drugs is highly problematic in the treatment of cancer. One reason for this is that a tumour is made up of cancer cells that are not all identical, for example some cells require more energy and oxygen to grow than others. As such, treating cancer is made very difficult as not all cancer cells will respond in the same way to a specific type of treatment.  One way of overcoming these problems is to combine different chemotherapeutic drugs.  This research aims to identify new treatment options for individuals with oesophageal squamous cell carcinoma (OSCC), one of the most common cancers affecting South Africans.

We are investigating the use of the drug metformin in combination with other chemotherapeutic drugs as the metformin stops the cancer cells from growing whilst the chemotherapy drugs kill the cancer cells. Metformin, which is currently used to treat diabetes, is currently under investigation as an anti-cancer treatment. In our research, we have found that OSCC cells stop growing when they treated with the drug metformin.  We have also tested metformin in combination with other chemotherapy drugs that are commonly used in the treatment of OSCC, these being cisplatin, 5-fluorouracil, and mitomycin c.  When we combine metformin with these chemotherapy drugs we show that some types of cancer cells show a better response and some types show a worse response.

We are currently investigating whether different combinations of drugs cause cancer cells to be destroyed by different mechanisms and therefore which drug combinations would be most useful in destroying the variety of cell types present in the tumour.

Manuscripts

Leonard Howard Damelin, Rupal Jivan, Robin Bruce Veale, Amanda Louise Rousseau, Demetra Mavri-Damelin.  Metformin induces an intracellular reductive state that protects oesophageal squamous cell carcinoma cells against cisplatin but not copper-bis(thiosemicarbazones).  BMC Cancer 2014, 14:314.

Damelin LH, Jivan R, Rousseau M, Veale R, Mavri-Damelin D. To be submitted to Molecular Cancer

Conferences

  • Jivan R and Mavri-Damelin D. The Synergistic Effects of Metformin and Cisplatin on Oesophageal Squamous Cell Carcinoma Cells. Molecular Biosciences Research Thrust Postgraduate Research Day, University of the Witwatersrand, December 2012.
  • Jivan R and Mavri-Damelin D. The Synergistic Effects of Metformin and Cisplatin on Oesophageal Squamous Cell Carcinoma Cells. Cross Faculty Postgraduate Symposium, University of the Witwatersrand, October 2012.

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