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07.10.15 Nobel Prize for Chemistry recognises discovery of DNA repair mechanisms

last modified Oct 09, 2015 09:01 AM
Chemistry Nobel Prize for groundbreaking research in field of DNA repair is basis for Gurdon Institute therapeutic success
07.10.15 Nobel Prize for Chemistry recognises discovery of DNA repair mechanisms

3-D structure of PARP1 protein. Credit Wikimedia Commons via CC-BY-SA 3.0

The three award winners, Tomas Lindahl, Paul Modrich and Aziz Sancar, made their discoveries on the enzymatic mechanisms of DNA repair several decades ago. That work laid the ground for other researchers to investigate the role of DNA repair in disease.

Certain cancers triggered by faulty BRCA1 or BRCA2 genes have problems in one of their DNA repair pathways. The Gurdon Institute's Steve Jackson set out to exploit the genetic vulnerability of such cells by developing drugs to block another DNA repair pathway that is controlled by an enzyme called PARP. Through establishing the Gurdon Institute spin-out company, KuDOS Pharmaceuticals, Steve's initiative led to the development of the clinically successful, orally administered PARP inhibitor olaparib (Lynparza), which kills cancer cells with faulty BRCA1/2 genes but not healthy cells of cancer patients that still have a working DNA repair mechanism.

As the Nobel Foundation's own background document on DNA repair says: 

"In fact, in many forms of cancer, one or more of these repair systems have been entirely or partially switched off...these sick cells are even more dependent on the repair systems that are still functioning; without these, their DNA will become too damaged and the cells will die. Researchers are attempting to utilise this weakness in the development of new cancer drugs...One example of a pharmaceutical that inhibits a repair system in cancer cells is olaparib."

Lynparza structure

Lynparza has been licensed for use in Europe and the USA against certain ovarian cancers, and clinical trials are still in progress in a number of other types of cancer.



Studying development to understand disease

The Gurdon Institute is funded by the Wellcome Trust and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.