A scientist works on a blood test in the Ajay Goel Lab, one of many labs that are developing blood tests to screen for different types of cancer.
Soon it may be possible to find different types of cancer earlier than ever through a simple blood test.
Among the many blood tests in development, researchers announced in July that they have developed one that may screen for early-onset colorectal cancer. The new potential screening tool, detailed in a study in the journal Gastroenterology, represents a major step in noninvasively and inexpensively detecting nonhereditary colorectal cancer at an earlier and more treatable stage.
In recent years, this type of cancer has been on the upswing in adults under age 50 and in those without a family history. In 2021, the American Cancer Society's revised guidelines began recommending that colorectal cancer screenings with colonoscopy begin at age 45. But that still wouldn’t catch many early-onset cases among people in their 20s and 30s, says Ajay Goel, professor and chair of molecular diagnostics and experimental therapeutics at City of Hope, a Los Angeles-based nonprofit cancer research and treatment center that developed the new blood test.
“These people will mostly be missed because they will never be screened for it,” Goel says. Overall, colorectal cancer is the fourth most common malignancy, according to the U.S. Centers for Disease Control and Prevention.
Goel is far from the only one working on this. Dozens of companies are in the process of developing blood tests to screen for different types of malignancies.
Some estimates indicate that between one-fourth and one-third of all newly diagnosed colorectal cancers are early-onset. These patients generally present with more aggressive and advanced disease at diagnosis compared to late-onset colorectal cancer detected in people 50 years or older.
To develop his test, Goel examined publicly available datasets and figured out that changes in novel microRNAs, or miRNAs, which regulate the expression of genes, occurred in people with early-onset colorectal cancer. He confirmed these biomarkers by looking for them in the blood of 149 patients who had the early-onset form of the disease. In particular, Goel and his team of researchers were able to pick out four miRNAs that serve as a telltale sign of this cancer when they’re found in combination with each other.
The blood test is being validated by following another group of patients with early-onset colorectal cancer. “We have filed for intellectual property on this invention and are currently seeking biotech/pharma partners to license and commercialize this invention,” Goel says.
He’s far from the only one working on this. Dozens of companies are in the process of developing blood tests to screen for different types of malignancies, says Timothy Rebbeck, a professor of cancer prevention at the Harvard T.H. Chan School of Public Health and the Dana-Farber Cancer Institute. But, he adds, “It’s still very early, and the technology still needs a lot of work before it will revolutionize early detection.”
The accuracy of the early detection blood tests for cancer isn’t yet where researchers would like it to be. To use these tests widely in people without cancer, a very high degree of precision is needed, says David VanderWeele, interim director of the OncoSET Molecular Tumor Board at Northwestern University’s Lurie Cancer Center in Chicago.
Otherwise, “you’re going to cause a lot of anxiety unnecessarily if people have false-positive tests,” VanderWeele says. So far, “these tests are better at finding cancer when there’s a higher burden of cancer present,” although the goal is to detect cancer at the earliest stages. Even so, “we are making progress,” he adds.
While early detection is known to improve outcomes, most cancers are detected too late, often after they metastasize and people develop symptoms. Only five cancer types have recommended standard screenings, none of which involve blood tests—breast, cervical, colorectal, lung (smokers considered at risk) and prostate cancers, says Trish Rowland, vice president of corporate communications at GRAIL, a biotechnology company in Menlo Park, Calif., which developed a multi-cancer early detection blood test.
These recommended screenings check for individual cancers rather than looking for any form of cancer someone may have. The devil lies in the fact that cancers without widespread screening recommendations represent the vast majority of cancer diagnoses and most cancer deaths.
GRAIL’s Galleri multi-cancer early detection test is designed to find more cancers at earlier stages by analyzing DNA shed into the bloodstream by cells—with as few false positives as possible, she says. The test is currently available by prescription only for those with an elevated risk of cancer. Consumers can request it from their healthcare or telemedicine provider. “Galleri can detect a shared cancer signal across more than 50 types of cancers through a simple blood draw,” Rowland says, adding that it can be integrated into annual health checks and routine blood work.
Cancer patients—even those with early and curable disease—often have tumor cells circulating in their blood. “These tumor cells act as a biomarker and can be used for cancer detection and diagnosis,” says Andrew Wang, a radiation oncologist and professor at the University of Texas Southwestern Medical Center in Dallas. “Our research goal is to be able to detect these tumor cells to help with cancer management.” Collaborating with Seungpyo Hong, the Milton J. Henrichs Chair and Professor at the University of Wisconsin-Madison School of Pharmacy, “we have developed a highly sensitive assay to capture these circulating tumor cells.”
Even if the quality of a blood test is superior, finding cancer early doesn’t always mean it’s absolutely best to treat it. For example, prostate cancer treatment’s potential side effects—the inability to control urine or have sex—may be worse than living with a slow-growing tumor that is unlikely to be fatal. “[The test] needs to tell me, am I going to die of that cancer? And, if I intervene, will I live longer?” says John Marshall, chief of hematology and oncology at Medstar Georgetown University Hospital in Washington, D.C.
Ajay Goel Lab
A blood test developed at the University of Texas MD Anderson Cancer Center in Houston helps predict who may benefit from lung cancer screening when it is combined with a risk model based on an individual’s smoking history, according to a study published in January in the Journal of Clinical Oncology. The personalized lung cancer risk assessment was more sensitive and specific than the 2021 and 2013 U.S. Preventive Services Task Force criteria.
The study involved participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial with a minimum of a 10 pack-year smoking history, meaning they smoked 20 cigarettes per day for ten years. If implemented, the blood test plus model would have found 9.2 percent more lung cancer cases for screening and decreased referral to screening among non-cases by 13.7 percent compared to the 2021 task force criteria, according to Oncology Times.
The conventional type of screening for lung cancer is an annual low-dose CT scan, but only a small percentage of people who are eligible will actually get these scans, says Sam Hanash, professor of clinical cancer prevention and director of MD Anderson’s Center for Global Cancer Early Detection. Such screening is not readily available in most countries.
In methodically searching for blood-based biomarkers for lung cancer screening, MD Anderson researchers developed a simple test consisting of four proteins. These proteins circulating in the blood were at high levels in individuals who had lung cancer or later developed it, Hanash says.
“The interest in blood tests for cancer early detection has skyrocketed in the past few years,” he notes, “due in part to advances in technology and a better understanding of cancer causation, cancer drivers and molecular changes that occur with cancer development.”
However, at the present time, none of the blood tests being considered eliminate the need for screening of eligible subjects using established methods, such as colonoscopy for colorectal cancer. Yet, Hanash says, “they have the potential to complement these modalities.”
In Ethiopia, Samuna’s three donkeys help her transport produce to market and to collect the water essential to her family, neighbours and livestock. Donkeys are more endangered than people realize, experts say.
“That's the reason why some breeds begin to disappear because humans were not really interested in having that specific breed anymore,” Gambini says. Nonetheless, in Africa, India and Latin America millions of rural families still rely on these hardy creatures for agriculture and transportation. And the only two wild donkey species—Equus africanus in Africa and Equus hemionus in Asia—are also dwindling, due to losing their habitats to human activities, diseases and slow reproduction rates. Gambini’s team wanted to create a way to preserve the animals for the future. “Donkeys are more endangered than people realize,” he says.
There’s much more to donkeys' trouble though. For the past 20 or so years, they have been facing a huge existential threat due to their hide gelatin, a compound derived from their skins by soaking and stewing. In Chinese traditional medicine, the compound, called ejiao, is believed to have a medicinal value, so it’s used in skin creams, added to food and taken in capsules. Centuries ago, ejiao was a very expensive luxury product available only for the emperor and his household. That changed in the 1990s when the Chinese economy boomed, and many people were suddenly able to afford it. “It went from a very elite product to a very popular product,” says Janneke Merkx, a campaign manager at The Donkey Sanctuary, a United Kingdom-based nonprofit organization that keeps tabs on the animals’ welfare worldwide. “It is a status symbol for gift giving.”
Having evolved in the harsh and arid mountainous terrains where food and water were scarce, donkeys are extremely adaptable and hardy. But the Donkey Sanctuary documented cases in which an entire village had their animals disappear overnight, finding them killed and skinned outside their settlement.
The Chinese donkey population was quickly decimated. Unlike many other farm animals, donkeys are finicky breeders. When stressed and unhappy, they don’t procreate, so growing them in large industrial settings isn’t possible. “Donkeys are notoriously slow breeders and really very difficult to farm,” says Merkx. “They are not the same as other livestock like sheep and pigs and cattle.” Within years the, the donkey numbers in China dropped precipitously. “China used to have the largest donkey population in the world in the 1990s. They had 11 million donkeys, and it's now down to less than 3 million, and they just can't keep up with the demand.”
To keep the ejiao conveyor going, some producers turned to the illegal wildlife trade. Poachers began to steal and slaughter donkeys from rural villages in Africa. The Donkey Sanctuary documented cases in which an entire village had their animals disappear overnight, finding them killed and skinned outside their settlement. Exactly how many creatures were lost to the skin trade to-date isn’t possible to calculate, says Faith Burden, the Donkey Sanctuary’s director of equine operations. Traditionally a poor people’s beast of burden, donkey counts are hard to keep track of. “When an animal doesn't produce meat, milk or eggs or whatever edible product, they're often less likely to be acknowledged in a government population census,” Burden says. “So reliable statistics are hard to come by.” The nonprofit estimates that about 4.8 million are slaughtered annually.
During their six to seven thousand years of domestication, donkeys rarely got the full appreciation for their services. They are often compared to horses, which doesn’t do them justice. They’re entirely different animals, Burden says. Built for speed, horses respond to predators and other dangers by running as fast as they can. Donkeys, which originate from the rocky, mountainous regions of Africa where running is dangerous, react to threats by freezing and assessing the situation for the best response. “Those so-called stubborn donkeys that won’t move as you want, they are actually thinking ‘what’s the best approach,’” Burden says. They may even choose to fight the predators rather than flee, she adds. “In some parts of the world, people use them as guard animals against things like coyotes and wolves.”
Scientists believe that domestic donkeys take their origin from Equus africanus or African wild ass, originally roaming where Kenya, Ethiopia and Eritrea are today. Having evolved in the harsh and arid mountainous terrains where food and water were scarce, they are extremely adaptable and hardy. Research finds that they can go without water for 72 hours and then drink their fill without any negative consequences. Their big jaws let them chew tough desert shrubs, which horses can’t exist on. Their large ears help dissipate heat. Their little upright hooves are a perfect fit for the uneven rocky or other dangerous grounds. Accustomed to the mountain desert climate with hot days and cold nights, they don’t mind temperature flux.
“The donkey is the most supremely adapted animal to deal with hostile conditions,” Burden says. “They can survive on much lower nutritional quality food than a cow, sheep or horse. That’s why communities living in some of the most inhospitable places will often have donkeys with them.” And that’s why losing a donkey to an illegal skin trade can devastate a family in places like Eritrea. Suddenly everything from water to firewood to produce must be carried by family members—and often women.
Workers unloading donkeys at the Shinyanga slaughterhouse in Tanzania. Fearing a future in which donkeys go extinct, scientists have found ways to cryopreserve a donkey embryo in liquid nitrogen.
TAHUCHA
One can imagine a time when worldwide donkey populations may dwindle to the point that they would need to be restored. That includes their genetic variability too. That’s where the frozen embryos may come in handy. We may be able to use them to increase the genetic variability of donkeys, which will be especially important if they get closer to extinction, Gambini says. His team had already created frozen embryos for horses and zebras, an idea similar to a seed bank. “We call this concept the Frozen Zoo.”
Creating donkey embryos proved much harder than those of zebras and horses. To improve chances of fertilization, Gambini used the intracytoplasmic sperm injection or ICSI, in which he employed a tiny needle called a micropipette to inject a donkey sperm into an egg. That was a step above the traditional IVF method, in which the egg and a sperm are left floating in a test tube together. The injection took, but during the incubating week, one after the other, the embryos stopped dividing. Finally, on day seven, Gambini finally spotted the exact sight he was hoping to see. One of the embryos developed into a burgeoning ball of cells.
“That stage is called a blastocyst,” Gambini says. The clump of cells had a lot of fluids mixed within them, which indicated that they were finally developing into a viable embryo. “When we see a blastocyst, we know we can transfer that into a female.” He was so excited he immediately called all his collaborators to tell them the good news, which they later published in the journal of Theriogenology.
The one and only embryo to reach that stage, the blastocyst was cryopreserved in liquid nitrogen. The team is waiting for the next breeding season to see if a female donkey may carry it to term and give birth to a healthy foal. Gambini’s team is hoping to polish the process and create more embryos. “It’s our weapon in the conservation ass-enal,” he says.
