It is a Monday morning, sometime in October 2022, and Prof. Laura Attardi, co-director of the cancer biology program at Stanford University School of Medicine, goes to work as usual. Before the COVID-19 pandemic, there would be dozens of staff and scientists at work. However, today, even the antechamber to her office, which has four desks, is empty.

Credit: Tomas Speight / Panther Media GmbH / Alamy

“In the past, before the pandemic, these desks were full on a typical weekday”, Prof. Attardi said. “I was expecting a new postdoc to start today, but she was not there. I knew that she was supposed to meet with a couple of people on our administrative staff, but there was no one from the administrative staff to ask in person”, she added. All communication had to be conducted through e-mail. Later that morning, for the first time since the start of the pandemic, Prof. Attardi will meet in person, rather than online, with her co-director. Among other topics, they will talk with a group of eight graduate students. But none of the students will be physically there — they are joining the meeting online. The shift to remote working, online communication and video meetings persists almost three years after COVID-19 appeared.

Despite the ongoing pandemic, life is almost back to normal in many parts of the world. The same can be said for cancer research — everything appears to be almost back to normal. Almost.

Challenges in research

Empty labs and offices and remote work are just some of the ripples left by the pandemic. The more profound impact was on cancer research. On one end of the spectrum, population-based and clinical research suffered the most, with many projects shutting down completely. “Those of us based at clinical sites were essentially unable to continue our research, as access to patients became extremely limited. Indeed, patterns of normal care were disrupted across the board. It became truly impossible to continue to perform any research, as the usual quality metrics and methods could no longer be implemented”, commented Prof. Karl Kelsey, from Brown University School of Public Health in the USA.

Fast forwarding to 2022, Prof. Kelsey says that “largely, patients have returned to the clinics, and we have been able to get back to work”, but certain aspects of clinical practice and referral are not yet back to normal. “I am talking about referral patterns and patterns associated with where patients seek care. This affects how one might seek to ascertain and study cases of a particular disease. Prior to the pandemic we knew where most patients might go to seek care, but this pattern may have shifted such that we need to adjust our methods so as not to miss cases”, he added.

Lockdowns, travel restrictions and other measures made it hard to recruit patients and to organize new trials, which usually involve international collaboration. A study that analyzed 1,440 oncology clinical trials across 91 countries found a 60% decrease in new trial launches during the pandemic period compared with pre-pandemic times1. Worldwide, it is estimated that around 1,200 trials were delayed between April and May 2020 (ref. 2). Analyzing regional effects, a study that interviewed 36 researchers conducting clinical trials for cancer around the world found that only 20% and 14% of respondents in the USA and Europe continued to enroll new patients, respectively3. A separate report that evaluated the impact of COVID-19 on clinical trials between 2019 and 2021 in Ireland found that patient enrollments fell by more than half across all trial types4. Trials involving radiotherapy suffered the most, with a 90% reduction in accrual that lasted more than 18 months. Various driving factors were identified, such as reduced staffing, delays in trial logistics and halting of enrollment and trial initiations due to safety concerns. According to Prof. Seamus O’Reilly, who led the study, patient accrual levels were up for the first three months of 2022 compared with the same period in 2021, but challenges such as staff recruitment and retention remain.

An exception to these disruptions involved clinical trials that had started before the onset of the pandemic, explains Prof. Andrew Redfern, Associate Director of the Harry Perkins Institute of Medical Research in Perth, Western Australia. “Our trial restrictions were partly a reduction of new studies as this is often an international effort where there was much disruption. However, all patients already on a study continued as usual”, he said. Children, for example, receive cancer therapies as part of their standard of care, explains Prof. Joost Lesterhuis, Head of Sarcoma Translational Research at the Telethon Kids Institute in Perth. Hence, government lockdowns did not apply and children’s access to therapies that were part of a clinical trial was not interrupted.

The pandemic also hindered the operation of laboratory-based research owing to disruptions in the supply chain for basic chemicals, equipment and maintenance, and the hiring and onboarding of staff. According to Prof. Antoni Ribas, former President of the American Association for Cancer Research (AACR) and Chair of the AACR Task Force on COVID-19 and Cancer, these issues continue to be a problem in 2022. “We are still feeling some of the negative impacts of the pandemic. It is hard to hire staff, especially for clinical trials, but also for laboratory work. Additionally, our research continues to be negatively impacted by supply chain issues affecting specific reagents and equipment — for example, I am still waiting for pieces of new equipment that were purchased a year ago”, he stated.

According to Prof. Peter Leedman, Director of the Harry Perkins Institute of Medical Research in Perth, “the biggest issues now would be supply chains and delays in getting key consumables, antibodies, core technologies, and so on, and still with recruitment of staff from out of state”. Prof. Xiaoting Zhang, Thomas Boat Endowed Chair and director of the breast cancer research program at the University of Cincinnati College of Medicine, in the USA, agrees that recruiting has not fully recovered from the pandemic. “It is better now compared to the last couple of years but is still very difficult to recruit PhD students and postdocs, although recruiting of principle investigators or volunteers remains stable despite the pandemic”, he said.

Not all researchers felt these disruptions to the same extent, however, with ‘dry labs’ lying at the other end of the spectrum. For example, Prof. Mieke Van Hemelrijck, a cancer epidemiologist from King’s College London, says that the pandemic caused little disruption to her research. Rather than shutting down her lab, she reorganized her research priorities, shifting the focus of her team towards COVID-19 projects.

For some research groups, the disruptions of lockdowns and restrictions everywhere meant more time for writing. “The lack of time spent in the lab in early 2020 provided researchers with the downtime to write and submit manuscripts. We saw a flurry of scientific papers in 2020 and early 2021 as a result”, stated Prof. Ricky Johnstone, Executive Director of Cancer Research at the Melbourne-based Peter MacCallum Cancer Centre (Peter Mac). Similarly, Prof. Van Hemelrijck says that during the peak of the pandemic, her group increased collaborations with clinical colleagues, which resulted in 40 new publications investigating COVID-19 and cancer from various angles. However, the halt in obtaining new data during lockdowns may have a toll in the future. “As the lockdowns continued, the data started to dry up. We will see a reduction in scientific output in the coming years because of the ‘data drought’ period that occurred due to the lockdowns”, she said.

Impact on funding

A major contributing factor to this predicted data drought involves money. Cancer Research UK, which supports about 50% of publicly funded cancer research in the UK, made cuts of around £45 million to its research budget during the peak of the pandemic. According to Prof. Karen Vousden, Chief Scientist at Cancer Research UK, these cuts can slow down future breakthroughs: “It has a knock-on effect. People who do basic research, fundamental research, a lot of them can answer very important and exciting research questions that are not necessarily cancer research questions. So we lose these very clever researchers, who think ‘you know, there’s no funding here. I’m going to start working on a different topic’. Will they ever come back to us?”. Indeed, some cancer researchers switched to COVID-19 research during the height of the pandemic, as reported here. The long-term impact this might have on existing lines of research is not fully understood yet.

In its most recent annual report, Cancer Research UK noted a reduction in the amount of research that it could fund compared with pre-pandemic levels. Similar funding issues were reported in the USA and Canada. The American Cancer Society (ACS), for example, raised $728 million in 2019, just before the pandemic started. In mid-2020, the ACS said that it expected to raise about $512 million for that year — a shortfall of $216 million from 2019. In 2020, the Canadian Cancer Society (CCS), Canada’s largest non-governmental cancer research funding agency, took the unprecedented step of canceling a major funding round for which 2,300 investigators had applied. In a 2020 statement for researchers, the CCS reported financial losses of $80–100 million, mostly due to event cancellations, drops in philanthropy support and reduced investment earnings. So far, no funding data have been reported for 2022 by the ACS or the CCS.

Lessons learned

But it is not all bad news. The pandemic taught us some lessons, and even led to some positive outcomes, as far as research goes.

COVID-19 forced us to find ways to advance clinical trials while protecting patients. In the USA, the Food and Drugs Administration (FDA) and the National Cancer Institute (NCI) established guidelines that included the use of remote technology to obtain patient consent or perform clinical assessments. Drugs were delivered to patient homes, and more flexibility was allowed in the use of laboratories and imaging centers outside of centralized facilities5. Similar changes occurred elsewhere. “The pandemic helped us discover the ‘power’ of tele-health and tele-trials. As tele-health was implemented, researchers saw the opportunity for tele-trials”, said Prof. Johnstone. “The profile and understanding of clinical trials and of medical research in general was elevated”, added Prof. Redfern, agreeing that: “the pandemic also majorly increased virtual and tele-medicine capacity such that we are now way better placed to carry out tele-trials for remoter patients”.

Another positive outcome involves creativity. Prof. Van Hemelrijck recalls that gaining ethics approval for even small projects used to take 18 months. But this changed during the pandemic. “We used to have to recruit patients to the hospital, but actually then we thought, well, hang on a second, we could also work with patient organizations and recruit patients through them, in which case we don’t have to go through ethics to the hospital. We go to the university, which is much quicker”, she said. A new (and long overdue) appreciation for epidemiologists and increased collaboration has also become apparent. “It’s been really good because our clinical collaborators appreciate much more why you need to work as a team with epidemiologists, statisticians, mathematicians to do collaborative research”, added Prof. Van Hemelrijck.

An additional benefit for cancer research has been a boost in certain lines of research. “The validation of mRNA technology for COVID-19 vaccines has provided the impetus to utilize similar technologies in the oncology space. Peter Mac has many new oncology projects using mRNA technology funded by mRNA Victoria”, explained Prof. Johnstone. Recently, the Australian state of Victoria struck a deal with the German biotechnology company BioNTech to further develop mRNA-based therapeutics, many of which are aimed at cancer. In the USA, Prof. Zhang is working on RNA nanotherapeutics to overcome breast cancer treatment resistance. Globally, others are pursuing similar goals. Recently, Merck and Moderna announced their goal to develop an mRNA-based cancer vaccine for patients with high-risk melanoma. Digital technologies also came to the fore during the COVID-19 pandemic response6. The increasing importance of such technologies in the cancer research space is underscored by the multiple start-up companies that are exploring the use of artificial intelligence for preventive medicine, cancer imaging and diagnostics.

The way ahead

A recent study identified seven key impacts of COVID-19 on cancer research7, including limited or halted research activity, forced adaptation of protocols, disruption to supply chains and the private sector, and impacted cancer diagnoses and services. The same study flagged delays to the progress of the field, but also the potential to develop new areas of interest and changes in research practice among the consequences of the pandemic on cancer research.

Global efforts now seek to understand the effects of the pandemic on cancer care and research. The COVID-19 and Cancer Global Taskforce, for example, aims to understand the impact of COVID-19 on global cancer research through its REPRISE project. The goal is to redefine priorities, particularly among low- and middle-income countries. In the USA, the AACR convened its own COVID-19 and cancer taskforce and this year published the ‘AACR Report on the Impact of COVID-19 on Cancer Research and Patient Care’, which included recommendations for science and policy8. Such initiatives are essential to make cancer research resilient to current and future pandemics, and to help the field adopt the positive lessons learned during the past few years.