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Professor Nicola Curtin is Professor of Experimental Cancer Therapeutics and team leader at the Northern Institute for Cancer Research at Newcastle University. She is also Editor in Chief of Expert Reviews in Molecular Medicine. Here she describes the childhood influences that drove her highly successful career in DNA damage research.

 

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Nicola has no problem identifying the source of her ambition, her father Bill Curtin. Despite leaving school at 14 he was determined to become an engineer, starting out as a teaboy and taking night classes. He became involved in building aerodromes during the war and subsequently became a lecturer at The Liverpool College of Building. He and his wife, Ella moved up from London and Nicola was born in Liverpool. In 1960, he established the engineering firm Curtins in their spare bedroom.  A lifelong communist and trade unionist, Bill instilled a strong sense of partnership and racial equality in the firm, which to this day is a highly successful employee-owned organisation.

Nicola’s intellectual prowess was well-hidden in her early years: she remembers coming 39th/40 in the class and failing her 11+ exam. Youngest and smallest in the class (she is now 4ft 11) and terrible at sports, it was only in her teens that she started to do better, driven by a love of biology, curiosity (her parents called her “Little Miss Why”) and a burning need to make the world a better place. Nicola hated to see sick people, so medicine was out, but wanted to improve people’s health and wellbeing so went to York University to read Biology. Initially doing an MSc at Manchester in 1977, she then did a PhD in hepatic carcinogenesis at the University of Surrey. She followed this with an extended trip around India and Southeast Asia before working in a lab at Newcastle University.  Here, through a collaboration with Adrian Harris, she became interested in thymidylate synthase and nucleoside transport inhibitors. When Adrian left Newcastle for Oxford in 1988, Hilary Calvert arrived and established the drug discovery team with Nicola as a key member. She felt this was an ideal way to fulfil her goal of improving people’s health.

She memorably overheard two Americans discussing career success at an AACR meeting and the importance of “sticking with one area (of research)”. She took this tip to heart and decided to focus on DNA repair and on the potential of PARP inhibitors in particular, identifying for the first time their synergy with topoisomerase inhibitors, as well as alkylating agents, such as temozolomide. Through the collaboration between the Drug Development team at Newcastle and Agouron Pharmaceuticals (subsequently taken over by Pfizer) increasingly potent inhibitors were developed, culminating in the clinical drug rucaparib (Rubraca®). In 2002 she established a collaboration with Thomas Helleday who had noticed that cells with defective base excision repair were dependent on homologous recombination, a concept known as synthetic lethality. Nicola immediately hit on the importance of this for using PARP inhibitors (which inhibit base excision repair) in patients with tumour-specific mutations in BRCA (essential for homologous recombination).  When the scientific PARP programme was shut down in 2003 in favour of its clinical use with temozolomide, Nicola persisted in her quest to explore synthetic lethality in BRCA. This culminated in her 2005 Nature paper with Thomas Helleday and their shared patent around tricyclic PARP inhibitors. It is this discovery that paved the way for PARP inhibitors to become mainstays in the treatment for ovarian, breast and other cancers.

After her Nature publication, Nicola was appointed as Personal Chair of Experimental Cancer Therapeutics. In 2019, Newcastle University sold royalties for their agent rucaparib (Rubraca®) for £31M. Famously, Nicola used her share of over £800K to establish the Curtin PARP (Passionate About Realising your Potential) fund at the Community Foundation, dedicated to supporting people who have lacked opportunities to gain confidence and qualifications. So far, the charity has donated over £100,000 to various individuals and groups, e.g. for young carers, and grants have supported Arts and Culture, Conservation and Environment and language skills to help asylum seekers finding work in the UK.  She has since been awarded the Robert R. Ruffolo Career Achievement Award from the American Society for Pharmacology and Experimental Therapeutics, was the first woman to be awarded the Biochemical Society’s Heatley medal and is an elected member of the Academy of Medical Sciences for her work in DNA damage repair.

Despite these successes, Nicola has no doubt she would have been more successful had she been a man. She has struggled with self-confidence and getting her opinions heard. She wishes she’d pushed herself further and sought programmatic funding early on. She remembers job interviews in which she was asked about her intentions to have a family as well as trying to keep her pregnancy secret in case it jeopardised the success of a grant application. Her daughter Helen was born in 1990 and, having taken 3 months of maternity leave, Nicola found the team’s preference for early morning or late-finishing meetings was non-conducive with parenting. Luckily, her engineer husband Tony was on hand to deal with drop offs to childminders and school. Her advice for the younger career woman: get a mentor, focus on one area of work, don’t get lumbered with too many administrative tasks and don’t let anyone exploit you or grind you down. Science requires imagination, detective skills, honesty and truth, which should never be sacrificed. You have to rely on your own resources and be determined and resilient. Ultimately, the best advice is clearly to channel your inner Bill Curtin and succeed despite the odds. Just do your best.