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How can short strings of nucleic acid lead to breast cancer drug resistance?

  • Researcher: Dr Anna Git
  • Institution: Cambridge University, Cambridge, England
  • Award Amount: £144,264 for 3 years from 1st January 2016
  • Cancer Type: Breast Cancer
How can short strings of nucleic acid lead to breast cancer drug resistance?
Breast cancer is the most common cancer worldwide and it claims more than half a million lives each year. Among the greatest challenges in its treatment is the resistance of some tumours or to chemotherapy. This often happens because the cancer increases the abundance of molecules that can inactivate the drug or expel it from the cell.

Dr Anna Git is studying RNA, a temporary copy of a small section of DNA, usually encoding instructions to make proteins. She told us "Some short RNAs, such as Vault RNAs (vtRNAs) do not code for protein, but are instead functional themselves. Of the four vtRNA types in the human genome, one can directly halt the growth of cancer cells. Two other types can attach to and seclude certain chemotherapeutic drugs, thus preventing their activity. Encouraging results have shown showed that altering the amount of vtRNAs in some lab-grown cancer cells substantially altered the cells' response to chemotherapy.

She explained "With my grant I propose to test how vtRNAs attach to a broad selection of drugs. I will also alter vtRNA levels inside cells to affect drug resistance in models of different types of breast cancer. Finally, I will identify proteins that recognise vtRNAs to understand how vtRNAs lead to drug resistance. In the future, I hope to help predict this mode of drug resistance in patients and perhaps avoid it altogether."

Why this research is important:

Chemotherapy remains our best weapon against many aggressive or advanced cancers. Unfortunately, the side effects of chemotherapy lay a heavy physiological, psychological and social burden on the patients and their families. If the tumour is resistant to the treatment, this burden is suffered in vain. While medical science has come a long way in understanding how chemotherapy works, we know far less about why it sometimes doesn’t. I hope that if I help understand which tumours are resistant to which chemotherapy I can help improve many patients’ quality of life by avoiding futile toxicity and allowing the earlier application of alternative treatments.
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