Aiming for the moon

The US launched a ‘cancer moonshot’ in 2016, aiming to achieve in five years what would otherwise have taken a decade in the battle against the disease. Bette Browne looks at what has been achieved so far and the
challenges that lie ahead

Former US Vice President Joe Biden, now in the midst of a bid for the White House, captured the imagination of many in the medical world three years ago when he launched President Barack Obama’s ‘cancer moonshot’. While no single dramatic development has emerged since then, experts say that significant advances are being made against the disease.

The title of the initiative may have seemed overly ambitious, recalling as it did President John F Kennedy’s successful pledge in 1961 to conquer space by sending a man to the moon and safely returning him to earth. Nevertheless, it should be remembered that President Kennedy’s moonshot goal ultimately took almost a decade to achieve and progress was made in incremental steps.

So, back in 2016, when the cancer initiative was launched with the aim of doubling the rate of progress in cancer prevention, diagnosis, treatment and care over a five-year period instead of over 10 years, it seemed an audacious mission. However, in December that year, to help make the ambitious idea a reality, Congress passed the 21st Century Cures Act, which allocated $1.8 billion to the initiative over seven years.

“The three overarching goals were to accelerate progress in cancer research, encourage greater collaboration, and improve the sharing of data,” Dr Dinah Singer of the US National Cancer Institute (NCI), which is managing the initiative under the auspices of the National Institutes of Health (NIH), told the Medical Independent (MI). “The foundation has been laid for achieving those goals.”

The NCI’s work has seen the launch of a series of scientific programmes and the awarding of over $600 million to research teams. “Cancer immunotherapy is one example,” Dr Singer said, “although progress in immunotherapy has been swift in recent years, the panel felt that, with an infusion of funds, even further advancement would be possible.”

Under the moonshot initiative, NCI is funding two groups of research teams: One focused on immunotherapeutic approaches in adults and the other in children. The Immuno-Oncology Translational Network — which includes 31 principal investigators at 19 different institutions — is investigating the mechanisms by which tumours in adults interact with the immune system, developing new immune-based therapies, and creating approaches for minimising the risk of side-effects.

Because most paediatric cancers are biologically quite different from adult cancers, a separate network of research teams has been established to focus on identifying immune targets and treatments specific to paediatric cancers and treatments and developing laboratory models for testing immunotherapies against these cancers.

Also built into the immunotherapy component is a data management centre, which will allow researchers to share their work easily and facilitate collaboration.

Another area in which significant progress is being made is in cancer prevention and early detection. Some of the research being funded in this area will make extensive use of implementation science — taking evidence-based interventions and testing ways to apply them in real-world settings. For example, several research teams will test ways to improve smoking cessation. Similarly, there are initiatives to improve the uptake of colorectal cancer screening. A moonshot-funded initiative is tackling this issue directly, with research teams conducting pilot studies of approaches to improve both screening and the clinical follow-up from that screening.

The moonshot is also focused on supporting fundamental research that will improve the understanding of cancer. One example is the Human Tumour Atlas Network (HTAN), a collaborative network that includes investigators at 10 research centres and one data management centre. Using a broad range of tools and technologies, these research teams will perform intensive analyses of tumour and tissue samples to construct three-dimensional maps of human cancers.

These maps will capture how cancers change over time — from a pre-cancerous lesion to established tumour, to resistant tumour, to metastasis — and describe the composition of the types of cells within and around a tumour and the genetic makeup of those cells.

Research teams will focus on highly-aggressive paediatric cancers, like neuroblastoma and glioblastoma, on cancer types like breast and lung cancers, and on cancers like that of the colon that often have a hereditary component.

Blue ribbon panel

The moonshot blue ribbon panel, of which Dr Singer was co-Chair, laid out a series of recommendations to help achieve the goals of the initiative. It emphasised that accelerating progress against a disease as complicated as cancer requires greater collaboration among researchers and a more efficient research process.

One recommendation, for example, was the creation of a network for directly engaging patients. The network’s aim is to make it possible for any patient diagnosed with cancer to have their tumours molecularly profiled and be pre-registered for any clinical trials for which they might become eligible.

An essential component of this patient network will be a biobank for storing tumour samples, other tissue specimens and associated patient data. Special emphasis will be given to include rare tumours. An NCI research team has already launched a pilot project, called NCI-CONNECT, for people diagnosed with rare central nervous system tumours. NCI wants to see research continuing “at a swift pace and help to achieve the rapid gains envisioned for this effort,” Dr Singer emphasised.

“With these new research initiatives, the moonshot is already well on its way to achieving its goals and having a lasting impact on cancer research. Everybody came together around this opportunity to see what we could do to accelerate our understanding of cancer for the benefit of patients. It has brought the community together and renewed a commitment to make a difference.”

ICPC and Pact

The NCI also launched the International Cancer Proteogenome Consortium (ICPC) that is breaking down silos through collaboration, co-operation, standardisation, data-sharing and investment among the world’s leading cancer and proteogenomic research centres. Proteogenomics combines proteomics with genomics to enable better insights into the molecular signatures present in cancer. Today, the initiative spans 12 countries and 31 institutions, with projects around 13 cancer types. Each institution has committed to the ICPC data-sharing pledge and to releasing data to the global research community.

As part of the cancer moonshot, in February 2018, the NIH and 12 pharmaceutical companies launched PACT, a five-year, $220 million research partnership to identify and develop standardised biomarkers and assays that will support selection and clinical testing of promising immune-oncology (IO) and combination therapies.

This includes both standardising existing biomarker assays and developing new, exploratory markers and assays so they can be used effectively in clinical trials.

Trump presidency

But not everyone is satisfied with the level of progress. Some suggest there is now less focus on the moonshot initiative under the administration of President Donald Trump, who succeeded Obama shortly after the cancer moonshot was launched. Others are concerned about funding cuts to the NIH, which they say will inevitably have an impact on cancer research within the agency, regardless of whether or not the research is directly related to the moonshot initiative, which is protected by congressional funding.

In his 2018 budget, for example, Trump proposed $5.8 billion in cuts to NIH funding, from $31.7 billion to $25.9 billion. “The President of the United States is not only not doubling down on our investment, he’s proposing draconian cuts,” Mr Biden said after the cuts were announced.

Biden initiative

Propelled by his concerns about the fate of the cancer moonshot under the Trump administration, the former Vice-President, along with his wife Dr Jill Biden, decided to launch his own private-sector ‘Biden cancer initiative’ in June 2017.

The battle against cancer has a very personal dimension for the Bidens, who lost a son, Beau, to brain cancer in 2015. “Every minute, every day matters to patients, and we must bring that same sense of urgency to cancer research and care systems,” the Bidens said in a joint statement at the launch of the Biden cancer initiative.

“We are joining everyone who spends their days thinking about preventing cancer, about better understanding its biological basis, about bringing early detection and education to all communities, about developing new treatments and therapies, and about caring for patients and their families through some of the hardest days anyone faces. We are on your team.”

The initiative, a continuation of the cancer moonshot, was under the auspices of the Biden Foundation. But on April 25, the Bidens stepped down from the Biden cancer initiative board when the former Vice-President announced his election bid. Subsequently, because of the election, the Biden Foundation itself suspended operations, apparently to avoid any of the financial and conflict-of-interest questions that shadowed Hillary Clinton during the 2016 presidential election, when her family foundation continued to operate and receive donations and grants while she was pursuing the White House.

With the foundation shuttered, many in the medical community were concerned about the fate of the Biden cancer initiative.

In an interview with MI, however, the Vice President of the initiative, Dr Danielle Carnival, made clear that its work is definitely continuing and there were ambitious plans for the future. She emphasised what had already been achieved and said Mr Biden, with whom she had worked closely in the White House during the Obama administration on the cancer moonshot, was optimistic about what could be achieved in the future.

“Even though the foundation has closed, we have decided to continue our work independently, though we still carry their name and include their vision for progress, but we do not currently have any connection with them,” she told MI.

“Our goal all along was to bring a sense of urgency to this issue and to bring new ideas and new perspectives into it that captured the idea of the original moonshot, and I think we’ve done that.”

She cited as an example that, at the Biden Cancer Summit in September last year, 57 new commitments were announced from the public and private sectors in response to the Bidens’ call for solutions to double the rate of progress against cancer. These initiatives focus on data-sharing, patient support, education, research, clinical trials, access to care, ending disparities, and prevention and early detection.

“So what we’ve started is what [former] Vice President Biden calls ‘a movement’. We need to approach this differently; we need to come together on this issue.

“Even if we never advanced new research, we believe there are people in the US and around the world who could be better served by a greater awareness about what we currently know about prevention, early detection and treatment of cancer who are not receiving the best of care today.”

While Congress earmarked funding for the Moonshot for seven years, Dr Carnival told MI she hopes that seven years will not be the end of the programme. “I certainly hope not. [Former] Vice President Biden has said time and again that cancer is a bipartisan issue; it affects everyone.

“The gains have been seen not just in the policies and programmes of the moonshot, but particularly on the research side. Getting a cancer diagnosis today is very different from what it was a decade and certainly two decades ago. Today, people are aware of immunotherapy and other treatments emerging that give you a different sense of hope and people know that they have more options. There have been a number of advances, for example, with biomarker-driven personalised cancer therapy.”  The first cancer treatment based on biomarkers was approved by the US Food and Drug Administration in 2017. The immunotherapy treatment pembrolizumab was successful in producing positive responses in patients with 15 different cancer types.

She said the moonshot was bringing a greater sense of urgency to the battle against cancer. “The reason [former] Vice President Biden did this was because he thought there was hope, even if not for his son, there were other people surviving longer and there were other people with other cancers who had much different prognoses than they would have had a decade ago.

“What we have done is bring people together to launch pilot projects and chip away at issues that are problematic in cancer care, like how data-sharing among cancer centres can be improved, how patients can have better access to their data, how patients can get better information about critical trials.”

Future

So what lies ahead for the cancer moonshot? “What we’re trying to do in the next 18 months is to look at the big issues that remain; we haven’t yet fixed the system. So in the next 18 months, we hope to focus on five or six big issues on how you would change the system — for patients to have better access to all these things; bigger-picture items such as having a nationwide patient navigation system. A standardised patient navigation system will help patients and their caregivers walk through the process, from treatment to reimbursement, and so on. At the moment, patients may have these systems but the standards looks different in different places. We need a gold standard and a robust system across the country. So we’re imagining the end-point and how to bring people together to that point.”

She believes the way forward lies also in more international collaboration, especially on the research side. “As we understand cancer more, it is more and more clear that from the scientific perspective, we are not going to understand all the particularities of specific cancers if we don’t have a bigger database across institutions, across countries, of what all of the cancers look like. I think there’s a willingness to co-operate as we understand more about cancers.”

She emphasised it was never the intention with the moonshot “that we would have one solution to the disease”. “Our goal was galvanising the energy, having a goal like the original moonshot did, not assuming that we’d get in one rocket ship and land on the moon in cancer terms. What we’ve already seen is that different solutions are chipping away at this big problem. The system was built for one magic bullet,” she said, citing how in 1957 Jonas Salk developed the first effective polio vaccine, “but that’s not how it’s going to happen [with cancer]. So we need to rebuild the system for the reality of how we are going to take on this task. Finding one solution for all of this means all of us coming together, sharing data, sharing patients’ experiences so we can better understand how to prevent, diagnose, treat and survive cancer.”

Dr Carnival is optimistic about future progress. “Absolutely. [Former] Vice President Biden started this because he was optimistic, despite his own experience [with his son’s death]. He discovered when he was going through treatments with his son that increased understanding was essential, collaboration and more co-operation. He says the reason he started this was not to give patients and caregivers false hopes, but that we’d have a real, true reason for hope, hope that there are real solutions around the corner, hope that there are new answers for prevention, that we reach more populations, that we’d decrease disparities, and hope that patients don’t have the same prognosis going in that his son had.”

Some are now hoping if Biden becomes the Democratic nominee and goes on to win the 2020 election, that the cancer moonshot will once again become a top priority within the White House. “We can’t claim victory until the solutions we are developing are the standard, not the exception, and until we have changed the things we cannot accept,” Mr Biden said recently about the battle against cancer.

While Ms Carnival emphasised she has no contacts with Mr Biden’s election campaign, she tells MI she believes the former Vice President was absolutely committed to the moonshot mission. “It’s no secret this is a priority for [former] Vice President Biden and he has said this is a mission that he and Jill plan on continuing for the rest of their lives, so I couldn’t imagine any administration that wouldn’t have a focus on that.”

Europe

Meanwhile, spurred on in part by the US initiative, Europe is now contemplating its own version of the cancer moonshot. The EU’s Research Commissioner, Mr Carlos Moedas, apparently wants to make a moonshot-style mission on cancer a centrepiece of the EU’s 2021-2027 research programme. He tweeted he wants “to tackle cancer on all sides by supporting more opportunities to fund cancer research”.

Crucially, Moedas is being supported in this endeavour by Mr Manfred Weber, the German MEP who is seen as a likely successor to Mr Jean-Claude Juncker as European Commission President later this year. Mr Weber says on his website: “I want Europeans to be the first ones to cure cancer. Imagine if we would combine all our resources, knowledge and databases.”

Like in the US, cancer is now the second-biggest cause of death in Europe and its incidence will inevitably rise with an ageing population, according to the World Health Organisation, with 1.9 million people dying from it each year. The most common cancers in Europe are breast, followed by colorectal, lung and prostate cancer.

However, there are competing ideas about what might constitute a European cancer mission and to what extent it might be modelled on the US moonshot.

“If you have money for this and you’re going to use it wisely, you don’t make a broad declaration that Europe is going to cure cancer, because that’s a fairly silly thing to say,” Prof Harold Varmus, Nobel-prize winner and former Director of the US National Cancer Institute and the National Institutes of Health told Science/Business recently.

Politicians must understand, he added, that there are no magic bullets and progress against cancer will continue to be incremental.

Prof Varmus’s statement almost exactly sums up the US cancer moonshot. The endgame, as Dr Carnival outlined, will be essentially about continually achieving incremental, but significant, progress through global collaboration. Indeed, putting Europe and the US on the same launchpad might be the next logical step in the global battle against this devastating disease.