Astronomy

A precision drug for prostate cancer may slow the disease’s spread

A drug used to treat breast
and ovarian cancers tied to certain genetic mutations may help combat some of
the most severe cases of prostate cancer.

Researchers tested the drug,
called olaparib, in a randomized clinical trial of nearly 400 men with advanced
prostate cancer and a mutation in one of several genes involved in repairing
damaged DNA, such as BRCA1 and BRCA2. These genetic defects raise the
risk of certain cancers, including breast and ovarian (SN: 4/7/15). Up to 30
percent of men with the hardest-to-treat prostate cancers also have mutations
in this type of gene.

In the Phase III clinical
trial, designed to compare the new treatment with current standard treatment, the
men were split into two groups based on their genetic mutations. The 245 men in
one group had mutations in some of the genes most commonly associated with
breast and ovarian cancer (BRCA1, BRCA2 and ATM), while the 142 men in the other group had other mutations in DNA-repair
genes. About two-thirds of men in each group took olaparib.

Overall in men given
olaparib, the disease progressed more slowly compared with those on standard
treatment drugs that deprive cancer cells of the male hormone testosterone. After
a year, about 22 percent of men taking olaparib had no signs that their cancer
was progressing, compared with 13.5 percent of men on the standard treatments, the
researchers reported September 30 in Barcelona at the European Society of Medical Oncology meeting.

The difference was greater
in the group with the BRCA1, BRCA2 and ATM mutations: 28 percent had no signs their cancer was progressing
compared with 9.4 percent receiving standard treatment. Alterations in the BRCA genes are often associated with
responding to drugs that work similarly to olaparib, says Maha Hussain, an oncologist
at Northwestern University Feinberg School of Medicine in Chicago who presented
the findings at the oncology meeting.

In patients with measurable
tumors within the BRCA group, tumor
sizes shrank in a third of those on olaparib, compared with 2.3 percent of those
on the standard therapy.

But while the new treatment
looks promising so far, potentially buying some patients a few more months, it’s
too early to say how the drug will impact overall survival. The clinical trial, cofunded by
pharmaceutical companies that manufacture olaparib, AstraZeneca and Merck &
Co, is slated to continue into early 2021.

Olaparib is a PARP inhibitor:
The drug blocks the PARP enzyme that repairs broken DNA. Cancer cells thrive in
a Goldilocks zone of DNA damage — just enough that the cells become carcinogenic, but
not so much that they die. Interfering with the PARP enzyme makes cells more
likely to go haywire and, eventually, commit cell suicide.

The drug works similarly in prostate
cancer as it does in ovarian and breast cancers. “Essentially, it’s going after
the same target: PARP,” Hussain says.

The U.S. Food and Drug
Administration has approved olaparib for breast and ovarian cancers, but not for prostate cancer. If the FDA one day approves
the drug’s use for severe cases of the disease, it will be one of the first
times that a precision medicine approach ­— or the idea of
personalizing a therapy based on a person’s genes ­­— has been used to treat prostate
cancer.

“[Prostate cancer therapy]
has been, generally, a one-size-fits-all approach,” Hussain says. “With regard
to precision medicine, I think that we’ve opened up the door.”

In the United States, 1 in 9
men will be diagnosed with prostate cancer in his lifetime, according to the
American Cancer Society. That makes the disease the second most common type of
cancer in American men, after skin cancer. It’s often treatable. Doctors can remove the prostate through surgery or destroy cancer
cells with radiation or chemotherapy. They may also use various drugs to decrease
male hormone levels or ramp up the body’s immune system to help fight the
cancer.

But, for some patients,
these therapies don’t work. About 30,000 men in the United States die from prostate
cancer each year.

“My hope is that we’re going
to be doing more and more research to better personalize care for the
individual patient,” Hussain says.

For patients with BRCA or ATM mutations, the researchers also found that olaparib appeared to
delay pain from worsening. After a year, about 80 percent of men reported that
their pain had stayed the same, compared with just over 40 percent of those
receiving the other drugs.

Almost all of the men,
regardless if they took olaparib or standard hormonal drugs, reported side
effects like anemia, nausea or fatigue. However, those on olaparib had higher
rates of anemia and reported more severe side effects.

The findings indicate that,
for patients with these specific mutations, a PARP inhibitor like olaparib may
work better than trying another type of hormonal therapy, says William Dahut, an
oncologist and the scientific director for clinical research at the Center for
Cancer Research in Bethesda, Md.

However, testing prostate
cancer patients for genetic mutations isn’t routine unless the cancer begins
spreading throughout the body, he says. “I think this will lead to many more men
being tested to see if they have these genetic abnormalities.”

If men are tested for these
genetic mutations very early on, then doctors may be able to predict which
patients might benefit from starting a PARP-inhibitor drug sooner. “It’s at
least possible that by using these drugs earlier, they may even have a bigger
impact,” Dahut says.

Organoids offer clues to how brains are made in humans and chimpanzees

Brainlike blobs made from chimpanzee cells mature faster
than those grown from human cells.

That finding, described October 16 in Nature along with other clues to human brain development, is one of the latest insights from studies of cerebral organoids — three-dimensional clumps of cells that can mimic aspects of early brain growth (SN: 2/20/18).

The new study “draws interesting parallels, but also highlights important differences” in the way that the brains of humans and chimpanzees develop, says Paola Arlotta, a neurobiologist at Harvard University who was not involved in the study. While “it’s still early days in the organoid world,” the results represent an important step toward understanding the particulars of the human brain, she says.

To make cerebral organoids from chimpanzees, researchers use
cells in blood left over from veterinarians’ routine blood draws. In the vials
were white blood cells that could be reprogrammed into stem cells, which
themselves were then coaxed into blobs of brain cells. “From that, we get
something that really looks a lot like the early brain,” says Gray Camp, a stem
cell biologist at the Institute of Molecular and Clinical Ophthalmology Basel
in Switzerland.

There were no obvious differences in appearance between the
chimpanzee organoids and the human organoids, Camp says. But a close look at
how genes behaved in the two organoids — and how that behavior changed over
time —
turned up a big difference in pacing. Chimpanzee organoids seemed to grow up
faster than their human counterparts.

At the same point in time, chimpanzee nerve cells, or neurons, were more mature
than human neurons, possessing a profile of gene behavior that’s known to come
with cellular age, the researchers found. That lag was “striking,” Camp says.
Compared with other species, human brains are known for taking a long time to
grow up, maturing through early life well past adolescence — a sluggish pace
captured by the organoids.

Aligning those different timelines of growth allowed
researchers to find genes that behaved differently in the two species, beyond simple
timing differences. Other analyses turned up differences in how stretches of
DNA were used. Some stretches are missing in people, but present in chimpanzees
and other primates. And in chimpanzees, those areas appeared poised for action,
perhaps ready to influence the behavior of certain genes, Camp says.

Although the human and chimp organoids offer clues about early brain development in primates, the brain blobs are still approximations of the real thing. Human brain organoids, for example, haven’t yet been able to capture a key trait of the human brain — its big neocortex, the outer layer of the brain involved in complex thinking, Camp says. Nor do these organoids re-create sophisticated connections between brain regions. Still, advances are coming fast (SN: 8/29/19). Studies of organoids hold promise, particularly for their ability to reveal developmental processes that would otherwise be hidden, such as the brain’s earliest days as it develops in the womb, Arlotta says.

Big dinosaurs kept cool thanks to blood vessel clusters in their heads

Massive dinosaurs came in
many different forms, but they all had the same problem: Staying cool. Now, fossilized
traces of blood vessels in the skulls of big-bodied dinosaurs reveal how different
dinos avoided heatstroke. Long-necked sauropods may have panted to stay cool, for
example, while heavily armored ankylosaurs relied on elaborate nasal passages.

Chemical analyses of fossil
sauropod teeth previously suggested that, despite their massive bodies, the
animals maintained body temperatures similar to those of modern mammals (SN: 6/23/11).
One possible explanation for this was thermoregulation, in which blood vessels radiate
excess heat, often with the help of evaporative cooling in moist parts of the
body, such as the nose and mouth.

To assess how giant
dinosaurs might have used thermoregulation, two vertebrate paleontologists from
the Ohio Center for Ecology and Evolutionary Studies in Athens mapped blood
vessel networks within fossil dinosaur skulls and skulls from dinosaurs’ modern
relatives, birds and reptiles. The researchers traced the networks in the bones
using computed tomography scanning that combines X-rays into 3-D images. Along
with data and observations from the modern relatives, those images let the scientists
map blood vessel patterns in the ancient animals. Dinosaurs from Diplodocus
to Tyrannosaurus rex each evolved their own ways to beat the heat, the team reports October 16 in The Anatomical
Record
.

Ankylosaurs had thick
clusters of blood vessels, representing cooling regions, primarily in their
noses. Sauropods had blood vessels clusters in their giant nostrils and mouths,
suggesting they used panting to stay cool. And fierce, large theropods like T.
rex
and Allosaurus may have used their sinuses. An extra air cavity connected
to their jaw muscles was also rich in blood vessels, the team found. Opening
and closing their jaws would have pumped air in and out of the sinus like a bellows.

Physicists have found quasiparticles that mimic hypothetical dark matter axions

An elusive hypothetical particle comes
in imitation form.

Lurking within a solid crystal is a
phenomenon that is mathematically similar to proposed subatomic particles
called axions
, physicist Johannes
Gooth and colleagues report online October 7 in Nature.

If axions exist as fundamental
particles, they could constitute a hidden form of matter in the cosmos, dark
matter. Scientists know dark matter exists thanks to its gravitational pull,
but they have yet to identify what it is. Axions are one possibility, but no one has found the particles yet (SN: 4/9/18).

Enter the imitators. The axions analogs
within the crystal are a type of quasiparticle, a disturbance in a material that
can mimic fundamental particles like axions. Quasiparticles result from the
coordinated jostling of electrons within a solid material. It’s a bit like how birds
in a flock seem to take on new forms by syncing up their movements.

Axions were first proposed in the
context of quantum chromodynamics — the theory that explains the behaviors of quarks,
tiny particles that are contained, for example, inside protons. Axions and
their new doppelgängers “are mathematically similar but physically totally
unrelated,” says theoretical physicist Helen Quinn of SLAC National Accelerator
Laboratory in Menlo Park, Calif., one of the scientists who formulated the
theory behind axions. That means scientists are no closer to solving their dark
matter woes.

Still, the new study reveals for the
first time that the phenomenon has a life beyond mere equations, in
quasiparticle form. “It’s actually amazing,” says Gooth, of the Max Planck Institute
for Chemical Physics of Solids in Dresden, Germany. The idea of axions is “a
very mathematical concept, in a sense, but it still exists in reality.”

In the new study, the researchers
started with a material that hosts a type of quasiparticle known as a Weyl fermion,
which behaves as if massless (SN: 7/16/15).
When the material is cooled, Weyl fermions become locked into place, forming a
crystal. That results in the density of electrons varying in a regular pattern
across the material, like a stationary wave of electric charge, with peaks in
the wave corresponding to more electrons and dips corresponding to fewer
electrons.

Applying parallel electric and magnetic
fields to the crystal caused the wave to slosh back and forth. That sloshing is
the mathematical equivalent of an axion, the researchers say.

To confirm that the sloshing was
occurring, the team measured the electric current through the crystal. That
current grew quickly as the researchers ramped up the electric field’s strength,
in a way that is a fingerprint of axion quasiparticles.

If the scientists changed the direction
of the magnetic field so that it no longer aligned with the electric field, the
enhanced growth of the electric current was lost, indicating that the axion
quasiparticles went away. “This material behaves exactly as you would expect,”
Gooth says.

Extreme snowfall kept most plants and animals in one Arctic ecosystem from reproducing

When Jeroen Reneerkens stepped off the plane in
Greenland, all he saw was white.

The avian ecologist at the University of Groningen in the Netherlands was expecting to find snowless tundra teeming with life, as he had each summer for nearly a decade. Reneerkens travels to Zackenberg Research Station in northeast Greenland to study sanderlings — slight, mottled-brown arctic shorebirds — as they and other migratory shorebirds noisily descend on the open tundra to breed each summer (SN: 11/13/18).

But when Reneerkens arrived in 2018, he found
only snow and silence. “There were no birds singing, even the river was still
frozen,” Reneerkens says. “I was shocked.”

A study published October 15 in PLOS Biology documents an ecosystem-wide reproductive collapse around Zackenberg in 2018. Most plants and animals, including everything from arctic foxes to tiny Dryas flowers, failed to reproduce that year, because an extremely snowy winter left much of the ground covered with snow well into summer, Reneerkens and colleagues found.

Climate scientists predict that, as the globe
warms, parts of the Arctic will
see more precipitation and more extreme seasonal fluctuations
(SN: 9/25/19). If years
like 2018 become more common, the authors warn that the consequences for the
ecosystem could be drastic.

“To see failure at so many levels of the food
web is highly unusual,” says Warwick Vincent, an arctic ecologist at Laval
University in Quebec City who wasn’t involved in the study. “Climate change is
all about extremes, and this is a compelling example of how we’re moving into a
world that’s less and less predictable.” 

For more than two decades, researchers at Zackenberg have carefully tracked the rhythms of arctic life. “There’s no such thing as a normal arctic summer,” says study coauthor Niels Martin Schmidt, an ecologist at Aarhus University in Roskilde, Denmark. But the snow usually melts in early June. “It’s like the lid gets pulled off the ecosystem, and everything starts,” he says.

Plants peek out of the soil and open their flowers to the long days. Hordes of insects emerge, pollinating plants and becoming food for migratory birds. Arctic fox cubs prowl bird nests looking for eggs, and stolid musk oxen birth calves that quickly join the herd.

“It’s a highly interdependent ecosystem that is
resilient to variability,” says Martin Schmidt, “but only to a point.” The extreme snowfall in
2018, more than double what many parts of the field site usually experience,
proved too much for the ecosystem, the researchers found.

Zackenberg Research Station
In 2018, vast amounts of snow at the Zackenberg Research Station in northeast Greenland (right) lasted long into summer compared with in 2013 (left), a drier year. Both photos were taken on June 10.Greenland Ecosystem Monitoring

By late July 2018, when the tundra around the
research station is usually in full swing, 45 percent of the landscape was
still covered in snow, entombing many plants and insects. While many plants
eventually did flower, their seeds didn’t have enough time to sprout before the
first freeze in August, the team found. Insects eventually emerged, but mostly too
late to be fed upon by migratory birds.

That meant that the sanderlings and other birds that had flown halfway around the globe from as far as Namibia expecting a feast arrived to slim pickings.

“Many birds must’ve turned back. We only
saw about a quarter of what we normally see,” Reneerkens says. The birds that
did arrive huddled close to the field station for food scraps. “They were
skeletons with some feathers,” he says, “Just super, super lean.”

Reneerkens found just one sanderling nest that
season, which hatched “ridiculously late” on August 5, he says. Normally, the
eggs would hatch in mid-July. Other birds fared just as poorly, and the few young
that did hatch probably weren’t healthy enough to survive the southward
migration, starting in later August.

Mammals were hit hard, too. The researchers saw
no arctic fox cubs, and almost no musk ox calves that season. The entire
ecosystem essentially came to a reproductive halt, Martin Schmidt says. “I try
not to be sentimental, but it was scary,” he says. “In nearly 25 years of
monitoring, we’ve never seen anything like this.”

One bad year, even this bad, doesn’t spell disaster for an arctic ecosystem. Plants and animals can reproduce again the next year, with few consequences. But the following summer swung towards the opposite extreme: Record high temperatures led to a much earlier snowmelt and then drier conditions in Zackenberg. The researchers worry that, as extreme events become more common, one bad breeding year could extend to two or three. “How many years in between do we need before the system collapses for real?” Martin Schmidt asks. “That we don’t know.”