Cancer blood tests getting closer to tissue biopsies in results
But researchers must first prove patients will live longer.
Brain cancer may be a good candidate for blood biopsies. Photo: Michelle Monje, M.D., Ph.D., Stanford University / NIH Flikr Image Gallery
One of the next big advances in cancer treatment will be the development of blood tests, called liquid or blood biopsies, that can monitor the growth of tumors by analyzing DNA shed from tumors into the bloodstream, several cancer experts tell Axios. Multiple research facilities and biotech companies are developing and testing these biopsies, but before they'll be seen in the clinic they need to lower the costs and prove the tests are reliable and lead to patients living longer.
The bottom line: The blood tests could help determine more precise treatments for cancers proven stubbornly hard to treat, like brain cancer. "In my opinion, there is very little doubt it will be" available soon, said Mark Roschewski, a staff clinician at the lymphoid malignancies branch at the National Cancer Institute. "Only question is when and at what breadth."
Where it stands: A significant amount of cancer research is now about fine-tuning the testing, lowering the genetic sequencing costs, and proving the clinical worth, Roschewski says. Shiuh-Wen Luoh, a medical oncologist at Oregon Health and Science University, agrees: "For today and tomorrow, it may stay in the academic arena."
The NCI is facilitating that effort with an initiative to advance the development and validation of liquid biopsy technologies. The institute aims to create a public–private partnership for engineers and clinical experts to work together.
Here's what cancer experts say about the benefits of liquid biopsies and where things stand:
What's new: A team of scientists this week announced a new approach for monitoring metastatic cancer DNA from blood samples that shows nearly 90% of the genetic features of a tumor can be detected in blood by sequencing all of the protein-coding genes (something known as whole-exome sequencing).
What they found: Their approach was effective for up to 49% of patients with advanced cancer. (It involves a two-step process of first screening potential participants and then running the whole-exome sequencing on those with 10% DNA in their blood sample.)
In order to screen the participants, the team first developed a new tool, called ichorCNA, which they used to. test 1,439 blood samples collected from 520 metastatic breast and prostate cancer patients.
Study author Viktor Adalsteinsson says ichorCNA is one way that costs for blood biopsies can be lowered because it ensures the right type of sequencing is applied to each sample, based on its tumor content.
Why this is important: Cancers respond differently in each person, and tumor DNA analysis may help to unravel what might work for a particular patient.
"We can now look not only gene-by-gene but throughout the entire cancer genome in order to figure out which treatments are right for which patient, and why some cancer cells don't respond to therapy. Doing so may inform better ways to treat the entire cancer and to prevent it from coming back," Adalsteinsson says.
Harvard's Flaherty, who was not part of the study, agrees. "The most astounding and important finding of this study is that tumors shed enough DNA into the bloodstream to permit an entire genomic profile to be generated. Just a few years ago, it was thought that this level of molecular analysis would only be possible by obtaining a sample of a tumor."
What's next: Luoh points out the study showed whole-exome sequencing only applies to one-third of metastatic patients, but there are new efforts to sequence even more minute amounts of DNA.
"If an approach like the one described in the Adelsteinsson paper could be made more sensitive then cancer could not only be detected earlier, but its molecular features could be ascertained at that same time and the appropriate therapy assigned," Flaherty said.
The big picture: NCI has a deep dive into how liquid biopsies are currently used to detect, track and treat cancer.
One of the transplant procedures (on left) that helped the patient (on the right). Photos: Ruhr-University Bochum
Scientists successfully used stem cell and gene therapy to replace 80% of the skin of a 7-year-old boy affected by an incurable genetic skin disease, they report Wednesday in Nature.
Why this matters: This is the first time researchers have been able to regenerate virtually the entire epidermis and also provides a blueprint for other stem cell and gene therapies. And, while the scientists cautioned more testing is needed to see if this could be used for the roughly 500,000 people worldwide with different forms of this particular disease, they said this experiment was a success.
"The kid is now back to school, is playing soccer and spending holidays with other kids," one of the study authors, Tobias Hirsch, said during a conference call with journalists.
The disease: The patient has junctional epidermolysis bullosa (JEB), which is a severe and often lethal genetic disease caused by mutations in one of three genes: LAMA3, LABM3 or LAMC2. The disease affects the protective outer layer of the skin, called the epidermis, but often not the inner layer, called the dermis. JEB makes the epidermis fragile, causing it to blister easily and eventually creating open untreatable wounds that can lead to infections, cancer and death. In his case, morphine was used to control the pain associated with the disease.
The patient's doctors, Hirsch and Tobias Rothoeft, reached out to Michele De Luca from the Centre for Regenerative Medicine at Unimore in Italy. De Luca, who in prior experiments had successfully grafted small patches of epidermis for a couple of patients, agreed to join them.
"[S]caling up the process should not be minimized. This is a huge undertaking and the fact that it worked essentially with the first grafts that were placed is pretty remarkable," George Cotsarelis, a dermatologist at the University of Pennsylvania who was not part of this study, told Axios.
What the researchers did: The team of scientists took a small biopsy from the part of the boy's skin without lesions, genetically corrected the LAMB3 gene, and grew a transgenic epidermal graft that contained a mix of stem cells (holoclones) and two other cell types: paraclones and meroclones. They did three separate grafts and tested the skin regularly to see how the skin changed, since skin tends to regenerate itself roughly once a month.
What they found: "His epidermis is stable, robust, and doesn't blister at all, and his functionality is quite good," De Luca said during the conference call. Hirsch added that as opposed to other graft patients, parts of the new skin on this boy shows some hair follicles and the patient does not need to use ointment, which is something other graft patients tend to require for the rest of their life.
De Luca said the recipe for success appears to be the combination of the three types of cells, with the stem cells as the key for long-term stability.
Follow up: Rothoeft said the patient went from "being on morphine the whole day to no drugs at all at the moment." He said the team is debating on whether they should replace the small percentage of the boy's skin that has not yet been grafted, since those areas continue to blister.
What it means for others: "The Herculean efforts required to perform this type of procedure make it difficult to imagine commercializing this approach. The regulatory burden and the costs are astronomical," Cotsarelis told Axios. De Luca says they currently have two clinical trials to continue advancing the safety and effectiveness of these transplants. However, he warned that other forms of the disease may not have the same response since "that involves another gene, another protein, another location."
A forest fragment. Photo: Carlos Peres
Human encroachment into forests that is parceling dense forestry into smaller and smaller areas called forest edges, is affecting 85% of forest vertebrates — sometimes positively (46%) and sometimes negatively (39%), an international team of researchers said in a study published in Nature Wednesday.
Why it matters: Study author Marion Pfeifer tells Axios it's "fair to say that we did not expect to find a relatively high proportion of species actually 'winning' when forest fragmentation occurs. However, we do emphasize that the species that lose out under forest fragmentation, i.e. the species we call forest core species...are more likely to be species that are already of conservation concern."
Study details: Funded by the EU's European Research Council, the team examined 1,673 species of arboreal vertebrates on five continents over a five-year period. They created and used two new measurements to quantify the abundance of each of the 1,673 species around the world and any chances determined by how close they were to the edge of forests.
"[This] is a powerful approach to examine patterns of biodiversity responses to forest edge effects. This mirrors approaches being used for examining effects of climate change projections or disease on species, but is novel for application to habitat fragmentation," Olson said.
Limitations and applications: However, Olson pointed out not all forests are simply an edge and a core. For example, she said in the Pacific Northwest forests of North America, changes in topography plus natural disturbances like landslides or fires make the forests more complex and potentially more sensitive to human-derived fragmentation. She says these areas should be studied further.
Threatened species, clockwise from top left: Antipodean albatross chick, Polynesian ground dove and the Mona iguana. Photos: Eleanor Briccetti, Marie-Helene and Tommy Hall / Island Conservation
In order to halt species extinction, researchers are suggesting conservation efforts should focus on islands, which hold 41% of the world's known highly threatened vertebrates, per a study published recently in Science Advances.
Why this matters: "Not only are species lost forever, never to be enjoyed or seen again, the decline of biodiversity has also affected human health, economics, food security, etc.," study author and conservation biologist Dena Spatz tells Axios.
What they found: "While islands make up only 5.3% of the earth's landmass, they are home to 41% of the world's highly threatened vertebrates. A disproportionate amount of threatened species," she says. Spatz, currently at the non-profit Island Conservation, says she finds it interesting that 95% of all the threatened species in the dataset occurred on at least one island with an invasive vertebrate. Islands with the most highly threatened vertebrate populations include Madagascar, Sri Lanka, Hispaniola and Cuba.
Good news: "While this may seem daunting, the good news is that there are proven techniques for dealing with the threat of invasive species...and thus management of invasives on these islands could benefit 39% of the Earth's highly threatened vertebrates," Spatz tells Axios.
More perspective: Robert Fisher, a conservation biologist with the U.S. Geological Survey, points out the study is based on highly threatened vertebrates as classified by the IUCN's Red List, which is incomplete. Fisher, who was not part of this study, says that IUCN so far has only assessed roughly 40,000 out of 61,000 vertebrates and the list does not include species that may be labeled as "data deficient" because they were only assessed once. "We should be investing a lot of money in exploration and discovery right now" to better determined which species are threatened, Fisher tells Axios.
Still, Fisher says the database is a good baseline tool in fighting the extinction of species, which has "cascading effects." An example of this is on Guam, where brown tree snakes were introduced and killed birds, which led to a huge increase in spider populations.This damaged tourism centered around birdwatching on the island and prompted concerns snakes could similarly invade Hawaii.
Doctors perform laparoscopic surgery using robotic arms while looking at a three-dimensional image from cameras inserted into the patient's abdomen. Photo: Mike Derer / AP
Two separate studies published Tuesday in the Journal of the American Medical Association suggest outcomes for robotic-assisted surgeries when compared with other minimally invasive surgeries were not significant enough to balance the higher costs and longer treatment times involved.
Why it matters: Expensive robotic-assisted minimally invasive surgery has become the trend in hospitals over the past two decades, as it allows for 3-D visualization and an enhanced range of instrument motion. However, there is limited rigorous evaluation of the effectiveness of this technology in clinical practice, according to Columbia University's Jason Wright, who wrote a JAMA editorial about the two studies.
Clayton Lau, chair of urology and urologic oncology at City of Hope National Medical Center, points out that one of the reasons the robotic-assisted surgeries were longer was because some of the surgeons were in a "learning phase." However, he suggests patients go to "centers of excellence" for these types of complex surgeries because the technology is still being developed.
U.S. standards: "The regulatory standards for new procedures and devices are much less stringent than for new drugs and often only require demonstration that a device is equivalent to some previously approved device," Wright said in his editorial. "There are numerous examples of how these challenges have resulted in widespread adaptation and use of new devices and procedures in routine clinical practice without rigorous evaluation."
Wright pointed to a new program called NEST that is being built by the FDA in order to help determine the efficacy of devices. Lau, who was not part of either study, agreed: "NEST will be important in evidence-based evaluation of all medical devices. This will help provide oversight and safety...[and] hopefully foster future innovation."
Stanford University's Benjamin Chung, one of the authors of the kidney study, told Axios: "There may be advantages to the robotic platform in the performance of this procedure that will be borne out with future endeavors that are driving the rapid adoption [of technology] and if so, these need to be identified."
Alessia Ranciaro, a senior research scientist at the University of Pennsylvania, collects a skin reflectance reading from a study participant from a Nilo-Saharan population. Photo: Tishkoff lab
Scientists have discovered new genetic variations in some African populations that influence skin color and suggest our earliest ancestors may have had a medium skin tone that later evolved to both darker and lighter tones seen in modern humans, per a five-year study published in Science Thursday.
Why this matters: Not only do the results alter the assumption that lighter skin evolved from the dark skin of ancestral humans, but they also help explain the vast range of skin color, identify possible patterns of human evolution and migration, and add to our understanding of human skin conditions like cancer and aging.
"To me, it has really changed some of the story about the evolution of skin color," Sarah Tishkoff, a geneticist at the University of Pennsylvania and leader of the international team, told Axios. Some of the variations in pigmentation genes appear to have originated roughly 1 million years ago, well before the emergence of modern humans, she said.
The study: The team used a color meter to read the level of melanin in the inner-arm skin of more than 2,000 people from Ethiopia, Tanzania and Botswana and sequenced genes from almost 1,600 of them. Later, a team confirmed their findings by testing the variations in zebrafish and mouse models.
The team found several novel variations (called alleles) in genes associated with pigmentation:
Migration implications: The data collected is consistent with there being an early migration event of modern humans out of Africa along the southern coast of Asia and into Australo-Melanesia, Tishkoff said.
Africa is key: "Many variances rose in Africa and some [of those] went to 100% frequency in Europe so it was only by going to Africa and looking at these variables" that they discovered some of these new genes, said Tishkoff, who calls herself a "major advocate" to increase all studies of genetics in Africa.
Go deeper: Listen to Tishkoff talk about the study on this Science podcast (9:55).
The "inexpensive" cream (on top) and "expensive" cream used in the study. Photo: Alexandra Tinnermann / Institute of Systems Neuroscience in Hamburg, Germany
Most people know about the placebo effect — when a person perceives, and then often receives, a beneficial health impact from a treatment that actually isn't directly addressing their condition. Studies have also shown people's perception of a higher-priced drug is that it will provide its remedy better.
Now, in a new study published Thursday, the flip side of that coin — called the nocebo effect — has been seen in people who reported worse side effects when given what they thought was a higher priced medicine.
Why this matters: "Understanding how nocebo effects work means that health care providers could actively use this knowledge in their way of talking to patients, how they explain things to patients and also which information to mention and to avoid in order to minimize the effect," one of the study authors, Alexandra Tinnermann, told Axios.
Study details: The team told 49 participants they were testing a prescription cream to relieve itch, and that one possible side effect was local skin sensitization, which could lead to increased pain perception. The group was divided into two groups — one to take an expensive-looking cream in a fancier box and the other to take a less expensive cream in a generic-looking box (both creams had no active ingredients).
The researchers then treated the participants with painful heat stimuli and recorded the neural activation in the brain and spinal cord.
Their findings: The participants who used the "expensive" cream reported a higher rate of pain that became more pronounced over time, compared to the participants using the "cheaper" cream. The researchers also determined the altered sensations due to perceived price were associated with differences in two particular brain regions (the periaqueductal gray and rostral anterior cingulate cortex).
Luana Colloca, a neuroscientist at the University of Maryland who was not part of this study, told Axios the study is interesting in how it shows the role the spinal cord and the two brain areas plays in switching pain on and off and the very real impact a person's perception can have on their pain levels.
"It's important [for clinicians and trial researchers] to know the words they use, the way they communicate, their behavior can raise perception of the side effects," says Colloca, who also wrote a perspective published with the study. She warned that in the past, misleading information about side effects led people to discontinue their treatment resulting in some of them dying from heart attacks or strokes.
Data: Trends and Patterns of Differences in Chronic Respiratory Disease Mortality Among US Counties, 1980-2014; Maps: Lazaro Gamio / Axios
Deaths from chronic respiratory disease rose by almost 30% from 1980 through 2014 in the U.S., with a large portion occurring in the Appalachia and Mississippi Valley, according to county-specific data study published Tuesday. The researchers examined the deaths of 80 million Americans, and found 4.6 million died from a chronic respiratory disease.
Biggest concern: The majority of those deaths was due to chronic obstructive pulmonary disease (COPD) in central Appalachia but can be found in other states in the southern half of the U.S. as far west as Colorado. David Mannino, who co-wrote an editorial about the study, pointed out mortality tended to occur in places where there is a high concentration of low-income, white individuals with current or historic tobacco use.
Why this matters: Chronic respiratory diseases became the fifth leading cause of death in 2015 and resulted in approximately $132 billion in health spending in 2013, the study stated. With county-level data, public health directives can be more targeted and, some experts hope, more effective in cutting death rates from the disease.
Outside observations: Michael Schivo, a pulmonary disease specialist who was not part of this study, said the rate of increased mortality is surprising due to strong public health intervention programs.
"This mortality imbalance may be due to lagging ramifications of smoking trends in middle-aged to older adults (those comprising the bulk of the population), but the data really suggest that anti-smoking interventions have not penetrated all areas of the country evenly. This has major implications for how we might change how public health interventions are allocated," Schivo said.
The numbers behind the 4.6 million deaths in that 35-year period (per 100,000 deaths):
Asthma: Deaths from asthma dropped nationwide by 46.5%, but certain areas, mainly along the southern half of the Mississippi River and in Georgia and South Carolina, showed an increased burden from asthma. Mannino said the the people in this area are mostly a poor, rural, and black population."This should be a focus of public health outreach," Mannino said.
Pneumoconiosis: This includes asbestosis, coal workers' pneumoconiosis, and silicosis, all of which declined except asbestosis. Most pneumoconiosis deaths occurred in central Appalachia but there were small pockets elsewhere. One interesting thing, Mannino pointed out, is that one of the areas where silicosis rose is where fracking occurs. "Deaths from silicosis should be completely preventable" once the new protocol on silica usages is adopted, he said. The Occupational Safety and Health Administration issued a warning and a final rule in 2017 to protect workers from silica dust.
NIAID scientists identify and isolate anti-HIV antibodies. Photo: NIAID
Two separate research teams showed a unique combinations of antibodies led to 100% protection from HIV-like viruses in test monkeys. They'll next enter human clinical trials, first testing their safety, in the hopes of eventually creating both a vaccine and therapies.
What they did: The two studies published Wednesday — one using a "first of a kind" antibody molecule that can bind to three different places on the HIV virus and the other using a cocktail of two single antibodies — state they believe the antibodies' ability to target different regions of the virus, which can mutate rapidly, prevented infection.
Why it is important: In the U.S., roughly 1.1 million people are living with HIV, and one in seven of them don't know it. The majority of new cases are reported in the South, showing a disparity of infection rates.
Study 1 details: NIH investigators working with the pharmaceutical company Sanofi created an antibody with three HIV-binding segments. "This has never been done before," NIH scientist and study author Richard Koup told Axios. By testing and finding the best performing combination of three antibodies and then combining them into one, they were able to effectively hit all the types of HIV virus they tested in monkeys.
Barton Haynes, an immunologist who was not part of the study, said the "new strategy in the case of the trispecific antibody for dealing with HIV diversity" was significant.
Added benefit: Another benefit to developing the trispecific antigen, Koup said, is that it could be applied to other resistant diseases, like cancer, Ebola, Zika, yellow fever and tuberculosis. Ebola, for example, has multiple strains that a single antibody may not cover but the trispecific antibody might be able to.
Study 2 details: A separate study (although some of the scientists overlapped between the two) developed a "cocktail" of two antibodies that together targeted different regions of the HIV virus and prevented 100% of the monkeys from becoming infected. These results were compared with using only one antibody, which resulted in little protection. "These data suggest that a combination antibody approach will likely be more effective than single antibodies for both prevention and treatment of HIV infection in humans, as a result of HIV diversity and resistance," study author Dan Barouch told Axios.
Yes, but: Koup warned that HIV vaccine and treatment protocol is still years away. "This is a major advance toward the development of a preventative strategy, but it's not a vaccine," Koup said. "We are still working toward the goal of creating a vaccine."
Hippocampal neuron in culture. Photo: Shelley Halpain / UC San Diego
A team of scientists announced Thursday they have discovered a new way the brain learns and stores information that may explain why people remember one-time events or new places.
What's new: For almost a half-century scientists have understood memories as being formed by neural connections that are strengthened by short repetitive stimulations, called the Hebbian rule. In the new study, researchers found a new method of learning (called BTSP) where memories can form in part of the brain over a longer time (seconds vs milliseconds) and without repetition.
Why this is important: It offers scientists a new way of looking at memory and could eventually inform our understanding of memory disorders. Julija Krupic, who published a perspective on this study in Science, wrote: "The authors have identified an intriguing new phenomenon...which eventually will tell us how we learn and remember new places and events that happen there."
What it means: Both processes likely play a part in memory formation. "Our study expands the repertoire of tools that neurons use to store information, and provides a mechanism for previously unexplained single trial learning of long event sequences," study co-author Aaron Milstein told Axios.
Why it makes sense: "Learning something new (e.g., a list of words) very often requires going over the material to be learned multiple times, and the more one repeats the material the better the learning and the subsequent memory... Nevertheless, and it is everyone's common experience, one is also able to form long-lasting memories with a single experience (e.g., remembering the name of a person just met or the address of a new restaurant)," Gianluigi Mongillo, of the French National Centre for Scientific Research who was not part of this study, told Axios.