Women in science: Cancer research pioneers – part 1

Headshots of Ruth Plummer, Eve Wiltshaw and Judith Bliss

Historically, science has never been an easy place for women to work. Gender stereotypes, lack of role models and male dominated cultures have made it harder for women to succeed in the field, to give just a few examples. And those that do make it tend not to receive the recognition they deserve.

While some progress has been made, with almost 40% of PhD students in science being female, women still only make up 11% of the most senior research roles in Europe. Clearly there is still a long way to go to break down these barriers and make the pathway to leadership more accessible.

That’s why, as our 20th anniversary year draws to a close, we want to celebrate some of the pioneering women who have contributed to impactful cancer research and paved the way for even more. In this first article we’re highlighting 3 women who have helped bring forward innovative new cancer treatments through their involvement in clinical trials.

Ruth Plummer

Professor Ruth Plummer

Professor Ruth Plummer is an oncologist who specialises in treating patients on experimental cancer trials and people with melanoma. She’s based in Newcastle where she also directs the Sir Bobby Robson Cancer Trials Research Centre, a unit specialising in early-stage clinical trials.

Some of her best-known work is related to a type of drug called a PARP inhibitor. These drugs stop cells repairing damage to their DNA. This can help to stop cancer cells repairing themselves, causing them to die.

In the late 90s at the University of Newcastle, Plummer was working with a team – funded by one of our predecessors, The Cancer Research Campaign – who were interested in trying to develop clinical PARP inhibitors. Originally it was hoped that PARP inhibitors might overcome resistance to some chemotherapy drugs, however subsequent research showed that cells in a dish were more vulnerable to PARP inhibitors if they already had problems with DNA repair caused by faulty genes such as BRCA1 or BRCA2. That’s particularly important because faulty BRCA1 and BRCA2 genes increase the risk of developing breast, ovarian, pancreatic and prostate cancer.

Once they had developed some promising compounds, Plummer and colleagues pushed towards testing these drugs in people for the first time.

The Centre for Drug Development, which was established by the newly formed Cancer Research UK to take risky projects through early phase clinical research, stepped in to sponsor the trial. And in 2003, Plummer became the first person in the world to write a prescription for a PARP inhibitor.

The trial tested a specific drug called rucaparib in combination with a chemotherapeutic agent in people with different types of cancer, including late-stage melanoma. While the trial was primarily designed to determine whether rucaparib was safe and didn’t cause too many side effects, the team also hoped that the drug might enhance the effects of the chemotherapy.

The study showed that the drug can indeed be safe and effective.

Since then, Plummer has continued her clinical research into PARP inhibitors, including applying to Cancer Research UK for funding to do the first ever BRCA-focused clinical trial with a PARP inhibitor.

PARP1 binding olaparib

There are a now a number of PARP inhibitors – including olaparib and rucaparib – licensed for people with BRCA-related ovarian, breast, fallopian tube, pancreatic and prostate cancers. Over 30,000 people have been treated with olaparib so far and that number is growing rapidly.

Plummer has also led the first clinical trials of inhibitors targeting proteins called ATR and MCT1. In healthy cells, ATR helps repair damage to DNA before the cells divide. MCT1 is sometimes more active than usual in some cancer types and plays a role in how cancer cells use energy.

Plummer was awarded a prestigious Fellowship from the Academy of Medical Sciences in 2018 for her outstanding contribution to experimental cancer medicine, and was awarded an MBE in the 2022 Queens Jubilee Birthday Honours for Services to Medicine. And we recognised her amazing work on PARP inhibitors with a Translational Cancer Research prize in 2010.

You can hear more from Ruth Plummer on our Cancer Research Matters podcast.

Eve Wiltshaw

Dr Eve Wiltshaw Credit: The History of Modern Biomedicine Research Group Queen Mary University London

Dr Eve Wiltshaw was a pioneer of medical oncology. Having joined The Royal Marsden and The Institute of Cancer Research in 1955, she helped establish The Royal Marsden’s Sarcoma Unit in the 1970s, which offered a specialised multi-disciplinary team to care for people with cancer – a rare concept at the time. She was also a key player in establishing some of the most widely used chemotherapy drugs.

In the early 1970s a team of our researchers in London confirmed that the platinum-containing molecule now known as cisplatin could target cancer in laboratory models, and also identified exactly which parts of the molecule made it so effective.

The next stage was to test it in the clinic. That wasn’t straightforward. Most clinical oncologists were sceptical of platinum-based drugs as heavy metal compounds were generally regarded as indiscriminate poisons, causing too many side effects.

But Wiltshaw believed in the strong anti-tumour properties demonstrated in the lab. She ran the clinical trials of cisplatin at the Royal Marsden Hospital, giving the drug to patients for the first time in the UK.

Despite challenging side effects, including kidney toxicity and nausea, they saw promising results in women with ovarian cancer.

Over subsequent years, cisplatin proved to be effective against several different cancer types. It continues to be used to treat some cancers today, including lung cancer. However, its unpleasant side effects sent researchers on a hunt for platinum-based cancer drugs that were just as effective as cisplatin but produced fewer negative reactions.

Both cisplatin and carboplatin are derived from platinum Credit: James St. John, CC by 2.0, via Flickr

Drug development efforts by our scientists led to the chemotherapy drug carboplatin. Wiltshaw was also involved in its clinical trials. Importantly, she led a study comparing carboplatin and cisplatin in people with ovarian cancer, which showed that carboplatin was just as effective as cisplatin, but with fewer side effects.

Carboplatin is now the most commonly used chemotherapy drug on the NHS. More than 26,000 people in the UK receive it every year.

In 1992 Wiltshaw was awarded an OBE for her outstanding contribution to cancer care. When Wiltshaw died in 2008 a memorial service was held in the Royal Marsden Chapel in Chelsea to commemorate her life.

Judith Bliss

Professor Judith Bliss

Professor Judith Bliss is another powerhouse of clinical trials. She leads the Clinical Trials and Statistics Unit at The Institute of Cancer Research (ICR-CTSU) where she was the founder Director. For many years she was also the Chair of the NCRI Cancer CTU Network Directors Group and is currently Chair of the UK Breast Intergroup.

As a statistician and trials methodologist she has worked throughout her career to promote the professionalism and role of academic Clinical Trials Units (CTUs). This involves working in partnership with clinical key opinion leaders to best utilise high quality research methods in the design, conduct and analysis of clinical trials. Her team provides that methodology leadership and operational delivery for clinical trials, mainly centred around improving treatments for breast cancer.

Her work has been instrumental in improving treatments for people with breast cancer. For example, working with leading clinical oncologists (Prof John Yarnold and others) she played a leading role in the START trials, some of the most influential radiotherapy breast cancer trials to date.

START showed that giving fewer but larger doses of radiotherapy is as safe and as effective at reducing the risk of cancer returning. People given fewer doses also had less side effects.

These results led the National Institute for Health and Care Excellence (NICE) to update its guidelines in 2009, recommending 15 fractions of radiotherapy after surgery for early-stage breast cancer, rather than the previously recommended 25.

This has had important implications for patients, reducing the number of hospital visits they have to make, saving time and money – and making the whole experience less stressful.

But this was just the start. Continuing to work in partnership with leading clinical oncologists Bliss’ team also led FAST-Forward, another practice-changing radiotherapy trial.

The results of this trial informed the Royal College of Radiologist’s emergency international COVID-19 pandemic guidance, that a schedule of 5 radiotherapy doses over a 1-week period should be put into immediate effect for people with early-stage breast cancer. As well as being more convenient for patients, this new standard of care has also helped to increase access to scarce radiotherapy resources.

But it’s not just radiotherapy, over the years Bliss has also worked on many systemic therapy trials. These include the recently published trials POETIC, which examined whether measuring a marker called Ki67 after 2 weeks of treatment with an aromatase inhibitor before surgery could be used to predict improved outcome for postmenopausal women with ER/PR positive invasive breast cancer, and plasmaMATCH, which aimed to show whether targeted therapies are effective in people with advanced breast cancer where the targetable mutation is identified through a blood sample.

The ICR Team who won the AACR 2022 Award Credit: ICR / soora.co.uk

Bliss’ team is now working on the PRIMETIME trial, again in partnership with the clinical oncology community. PRIMETIME aims to use biomarkers to identify people at low risk of breast cancer recurrence and determine whether radiotherapy can be safely avoided in these groups.

Bliss was recently successful in renewing her prestigious NIHR Senior Investigator Award and she was also part of the team that were awarded the 2022 Team Science Award from the American Association for Cancer Research (AACR).

Paving the way

These are just a few of the women who have made valuable contributions to cancer research. As well as helping to improve outcomes for people with cancer, these women are role models for female researchers of the future.

Stay tuned for part 2, where we’ll be highlighting more female researchers who have done pioneering research in the field.

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