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Prof Steve Jackson of Gurdon Institute wins prestigious European cancer research prize


By Paul Brackley


His work has led to important new cancer medicines and given us a greater understanding of how our DNA repairs itself.

Professor Steve Jackson of the Wellcome / Cancer Research UK Gurdon Institute in Cambridge (7226479)
Professor Steve Jackson of the Wellcome / Cancer Research UK Gurdon Institute in Cambridge (7226479)

Now Professor Steve Jackson, of the Wellcome/Cancer Research UK Gurdon Institute in Cambridge, has won a prestigious European cancer research prize.

He will receive the ARC Foundation's Léopold Griffuel Award, worth 150,000 euros, at a ceremony in Paris in April.

Prof Jackson said: “I am deeply honoured and delighted to be given this prestigious award for my research, which has been translated into patient benefit.

“The field of DNA damage repair has expanded substantially in recent years and continues to provide us with new avenues for understanding the causes of cancer, and identifying new therapeutic targets.”

Prof Jackson’s research was important in developing medicines such as PARP1 and 2 inhibitors, currently used for cancer treatment.

His lab’s latest work, published last month in Nature Communications, was important for understanding cancer drug resistance in sporadic cancers, and highlighting potential therapeutic targets for the genetic disease, ataxia-telangiectasia.

Collaborating with colleagues at AstraZeneca, researchers in Prof Jackson’s lab identified mechanisms by which drug sensitivities characteristic of cells deficient in the ATM gene can be counteracted by changes in other genes.

Mutations in the gene cause the devastating neurodegenerative and cancer predisposition disease called ataxia-telangiectasia (A-T), and are associated with various forms of sporadic cancer.

Other work has shown the ATM protein, produced from the ATM gene, acts as a “molecular guardian of the genome“ by detecting DNA damage and promoting its repair.

This means A-T patients and ATM-deficient cells are hyper-sensitive to endogenous DNA lesions that can lead to neurodegeneration, and also to DNA-damaging agents used in cancer therapy such as PARP inhibitors, meaning they do not work effectively.

The latest study used the CRISPR-Cas9 genetic screening technique to show that defects in the products of several genes also involved in DNA repair pathways can alleviate the hypersensitivity of these cells to PARP inhibitors and the chemotherapeutic drug topotecan.

The work suggests how cancers with ATM mutations might evolve resistance in the clinic and how these resistant cancers may be susceptible to other anti-cancer agents. It also indicates potential therapeutic targets for A-T.

Dr Josep Forment, oncology team leader at AstraZeneca, who is co-lead and co-corresponding author of the study, said: “It has been wonderful collaborating with the group of Prof Steve Jackson to carry out these exciting studies.”

Prof Jackson said: “This study marks a major step forward in our understanding of how the ATM protein maintains genome stability and how ATM defects can cause cancer and neurodegeneration in human patients with A-T. My colleagues and I are very excited by the potential clinical applications for our findings, which we now plan to actively pursue in my laboratory and with our colleagues elsewhere.“

Prof Jackson’s award came in the translational and clinical research category.

Fondation ARC is the largest French foundation dedicated to cancer research, and is funded by public donations. Its ambitious goal is “to cure two cancers out of three by 2025”.

The award was created according to the will of the late Mrs Griffuel by bequest, in honour and memory of her late husband, Léopold Griffuel.

The other winner, in basic research, was Prof Laurence Zitvogel, of UMR Inserm, for her research in immunology, which improved the understanding of the biological mechanisms of the anti-cancer immune response and immunotherapies. Prof Zitvogel’s discoveries have changed the way the immune system is understood in relation to cancer treatment.

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