Will the U.S. Cancer Moonshot program land its target to halve cancer death rates?  

Cancer Moonshot

It was predicted that more than 600,000 people would die from cancer last year in the U.S., according to the American Cancer Society. But what if those figures could be halved over the next couple of decades? Although no small feat, that’s precisely what the Cancer Moonshot program aims to do. 

The White House initiative, which was reignited by the U.S. President Joe Biden last year, looks to crank up therapeutic research and foster collaboration. With the goal of slashing the cancer death rate by 50% within 25 years, the U.S. Advanced Research Projects Agency for Health (ARPA-H) offers grants to scientists committed to cancer research, as part of the program.

One year into the scheme, Richard Edelson, Professor of Dermatology at the Yale School of Medicine in Connecticut thinks that it could “change medicine as we know it.”

“The Moonshot Program encourages the right scientists to think really big,” said Edelson, who is a co-principal investigator on the project that won the first ARPA-H grant.

Cancer Moonshot: how did it all come about?

The program was initially launched in 2016, at the time of Barack Obama’s presidency, where $1.8 billion was allotted for the initiative. The funds were key to driving more than 240 research projects and 70 programs in the field of cancer treatment and prevention. The Blue Ribbon Panel – which consisted of experts from the scientific community – was set up to advise the Cancer Moonshot Task Force. They created a report on achieving the goals that the program had set out for. 

This involved encouraging more patients to join clinical trials and establishing an immunotherapy network in order to better understand why certain people with cancer respond well to immunotherapies and some don’t, as a means to come up with ways to combat cancer resistance. It also sought to create a 3D cancer atlas that consisted of maps of the cellular interactions that lead to the formation of tumors.

With the revamp of the initiative last year, and a lofty target ahead, it aims to tackle disparities in cancer screening, especially since COVID-19 put a damper on attending screenings, delaying diagnosis, which can make it quite hard to treat the cancer at later stages. Moreover, the American Indian Colorectal Cancer Screening Consortium was launched to develop a deep learning algorithm that was capable of analyzing cervix images using a smartphone, presenting a more affordable option for cervical cancer screening.

And, in a bid to address how the lack of insurance  – where over 90% of the U.S population rely on insurance to cover healthcare costs, according to Statista – can affect a patient’s access to cancer care, an insurance support tool that integrates into health records to aid staff at healthcare centers to get patients to enroll for health insurance, was developed. 

To add to that, a study found that transportation is a significant barrier for people who need a colonoscopy to complete their colorectal cancer screening. As a result, a rideshare system is being looked into to boost cancer screening rates across the country. 

First Cancer Moonshot grant awarded to Yale’s cancer vaccine project 

As the program strives to tackle the rising cancer cases, the ARPA-H – which was born out of the Defense Advanced Research Projects Agency (DARPA) that pioneered the internet – grant projects which sprung from it, intend to do the same. 

Titled ‘Curing the Uncurable via RNA Encoded Immunogene Tuning,’ Edelson’s project aims to develop cancer vaccines based on mRNA technology – popularized by its use in COVID vaccines. But there’s more to it than meets the eye. The team at Yale has uncovered the workings of the “master-switch” of the immune system, the dendritic cells.

These cells, which make up less than 1% of cells in the blood, interact with T cells to trigger an immune response in the body. They circulate in the form of its precursor, a common white blood cell called monocyte, explained Edelson. When people are infected with a new virus or bacteria, and even in the earliest stages of cancer, the dendritic cell somehow gets to the spot, and destroys the cancer or the pathogen. 

Although these cells have “tremendous promise,” even 50 years after the discovery of this cell, no dendritic cell-based treatments have been successful, simply because how monocytes evolve to become dendritic cells was not known. Until now.

“Over the last 10 years, we cracked the code,” said Edelson, who had cured a patient’s blood cancer 40 years ago, after he had accidentally landed on the way monocytes become dendritic cells, which led to expedited research in the field.

“Once we knew that, we now could make lots of dendritic cells very quickly from anybody. And program them to initiate targeting of the cancer in a patient-specific way,” said Edelson, who founded the Yale spin off Transimmune, which specializes in cancer treatment.

Although the therapy is now given at almost every medical center in the U.S., this project is on a mission to treat all kinds of cancers, including solid tumors, which unlike blood cancers, are harder to treat via immunotherapy because antigens are not easily found in the blood. That’s where the mRNA comes in. 

“So, RNA extracted from the tumor can serve as a GPS directing immune attack of the tumor,” said Edelson. 

“mRNA as a preventive tool does nothing by itself. When you get a shot of an mRNA-based vaccine in your shoulder, it’s easy for the public to merely think that the next steps towards vaccination are automatic. In reality, the mRNA alone does nothing. It needs to find, enter and commandeer the machinery of the right cell,” he said. “And it is that right cell which then engineers the vaccination. So the real captain of the team in that tandem, is the (dendritic) cell.  With respect to COVID vaccinations, it is not fully clear how and even where that happens.”

Researchers will start out by extracting all the mRNA from the cancer and feeding it into the dendritic cell – which are antigen presenting cells – which will then sort the RNA to identify the needle out of the haystack – the antigen – explained Edelson.

“Because we were able to do it with the whole cell, we see no reason why we won’t be able to do it with the RNA. But that’s still the big challenge that we hope to solve within the next year or two.”

As part of the grant, $25 million was awarded to the team at Yale, Emory University and the University of Georgia, who are collaborating on this project.

Meanwhile, researchers at Stanford University have bagged over $26 million for their project that plans to bioprint a human heart and implant it in a living pig within five years. While this may seem like quite the moonshot, the 3D printing field has been making its mark across various fields of biomedicine. The ARPA-H-funded project will use bioreactors that will churn out billions of cardiomyocytes (heart muscle cells), ultimately generating enough cells to create a heart every two weeks. The heart will then be transplanted into a pig, which someday, the team plans to replicate in humans, using a patient’s own stem cells.

As Edelson pointed out that breakthroughs in research are often fueled by “big ideas,” he said: “You can’t apply to ARPA-H with an idea which doesn’t have potentially very large value. And that idea must be grounded in sufficiently strong science to pass close scrutiny.”

Hurdles along the way

While the program is addressing “the myriad of challenges faced by the research community that ultimately influences care,” which includes data sharing, open access to publications, information, and tissue banks that reflect the diversity of the public, according to Mona S. Jhaveri, cancer researcher and founder of Music Beats Cancer, it is not without its challenges.

“I think the goal of reducing cancer deaths by half is quite ambitious and will require much more. For example, Moonshot does not currently help the innovation community, where access to early-stage funding is paramount to advancing biomedical technologies,” said Jhaveri. “Innovators continue to be underrepresented and underfunded by government cancer-fighting initiatives, yet their role is critical.”

More needs to be done to spur lifestyle changes as well. As obesity is a health concern that affects more than 40% of Americans, according to the Centers for Disease Control and Prevention, it has been linked to many deadly cancers including pancreatic, liver and ovarian. Jhaveri believes that little has been done to lower obesity rates.

And, while the program aims to nip nicotine addiction in the bud, through its smoking cessation program, it may not be enough to get people to quit smoking, which is the largest driver of cancer deaths in the country. As the program only budgets $15 million over five years for that initiative, it needs more money to make a significant impact, according to Sean Marchese, a registered nurse at The Mesothelioma Center and oncology medical writer. Besides, with the U.S. Food and Drug Administration (FDA) delaying nicotine reduction rules, Marchese explained that this would affect the sales of flavored cigarettes and cigars.

However, Marchese believes that the program is still making strides in cancer prevention, although it could do with more transparency. “While a decrease in the number of smokers would significantly impact cancer deaths, other initiatives from the Cancer Moonshot are also progressing slowly. Funding for blood tests and screening programs is helpful, but it will take years to see results, and details on the financing could be more transparent. Perhaps, the most direct impact comes from support for emerging technologies and funding to cancer centers,” said Marchese, who thinks that the ARPA-H grants could be a step in the right direction.

“This type of backing and actionable support for cancer centers and caregivers will have immediate and direct benefits for most patients who need new therapeutic options.”

The program may seem far-fetched to some because of the growing number of cancer cases currently, coupled with certain cancers becoming relentless over time, but as the saying goes, shoot for the moon, and you’ll land among the stars.

Edelson said: “I would not be doing this if I didn’t think we could win. The proof will be when it happens. And I’m very grateful to ARPA-H saying they think there’s a good chance we can do it… Having a vaccine that can be personalized and made for people in two hours sounds like a long shot. But, in actuality, since we have already done it in one cancer and have mastered key required steps, we like our odds. To have arrived at this threshold is a thrill to me. I’ve had a lot of excitement in my career, but I’ve never been involved in anything quite like this.”

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