Science
New strategy to fight aggressive brain tumor shows promise
A new strategy to fight an extremely aggressive type of brain tumor showed promise in a pair of experiments with a handful of patients.
Scientists took patients’ own immune cells and turned them into “living drugs” able to recognize and attack glioblastoma. In the first-step tests, those cells shrank tumors at least temporarily, researchers reported Wednesday.
So-called CAR-T therapy already is used to fight blood-related cancers like leukemia but researchers have struggled to make it work for solid tumors. Now separate teams at Massachusetts General Hospital and the University of Pennsylvania are developing next-generation CAR-T versions designed to get past some of glioblastoma’s defenses.
“It’s very early days,” cautioned Penn’s Dr. Stephen Bagley, who led one of the studies. But “we’re optimistic that we’ve got something to build on here, a real foundation.”
Why don’t we have tails like our ancient animal ancestors? Scientists finally have an answer
Glioblastoma, the brain cancer that killed President Joe Biden’s son Beau Biden and longtime Arizona Sen. John McCain, is fast-growing and hard to treat. Patients usually live 12 to 18 months after diagnosis. Despite decades of research, there are few options when it returns after surgery and radiation.
The immune system's T cells fight disease but cancer has ways to hide. With CAR-T therapy, doctors genetically modify a patient’s own T cells so they can better find specific cancer cells. Still, solid tumors like glioblastoma offer an additional hurdle — they contain mixtures of cancer cells with different mutations. Targeting just one type allows the rest to keep growing.
Mass General and Penn each developed two-pronged approaches and tried them in patients whose tumors returned after standard treatment.
At Mass General, Dr. Marcela Maus’ lab combined CAR-T with what are called T-cell engaging antibody molecules — molecules that can attract nearby, regular T cells to join in the cancer attack. The result, dubbed CAR-TEAM, targets versions of a protein called EGFR that’s found in most glioblastomas but not normal brain tissue.
Penn’s approach was to create “dual-target” CAR-T therapy that hunts for both that EGFR protein plus a second protein found in many glioblastomas.
Both teams infused the treatment through a catheter into the fluid that bathes the brain.
Mass General tested three patients with its CAR-TEAM and brain scans a day or two later showed their tumors rapidly began shrinking, the researchers reported in the New England Journal of Medicine.
“None of us could really believe it,” Maus said. “That doesn’t happen.”
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Two of the patients' tumors began to regrow soon and a repeat dose given to one of them didn’t work. But one patient’s response to the experimental treatment lasted more than six months.
Similarly, Penn researchers reported in Nature Medicine that the first six patients given its therapy experienced varying degrees of tumor shrinkage. While some rapidly relapsed, Bagley said one treated in August so far hasn't seen regrowth.
For both teams, the challenge is to make it longer-lasting.
“None of this is going to matter if it doesn't last,” Bagley said.
BAU researchers develop accurate method for identifying livestock diseases
With the use of DNA testing, a Bangladesh Agricultural University (BAU) research team led by Dr. Md. Shahiduzzaman,Professor of Parasitology, has developed a method for identifying various diseases in livestock caused by blood protozoa with almost one hundred percent accuracy.
Conducted under the auspices of the Bangladesh Agricultural Research Council (BARC), the research initiative involved testing nearly five hundred samples from various farms in Sirajganj and Rangpur to develop this method.
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Dr. Shahiduzzaman informed that in Bangladesh, livestock are particularly susceptible to blood protozoa like Babesia, Theileria, and Anaplasma. These pathogens lead to weight loss, reduced blood and milk production and even death if not treated properly.
Dr. Shahiduzzaman also stated that incorrect diagnosing of these diseases at the field level often leads to incorrect treatment, as symptoms of such diseases are usually similar. In some cases, the presence of pathogens in the blood of infected animals is determined through antibody and antigen tests in the laboratory. However, even with these methods, achieving one hundred percent accurate diagnosis is not always possible.Regarding his disease identification method, Dr. Shahiduzzaman explained that blood samples from animals are first collected, and then DNA is extracted. The extracted DNA is then tested using a PCR machine. Even though a small amount of parasite DNA is present in the sample, it can still be easily detected in this test.
Since the process is sensitive to PCR, almost one hundred percent accurate results can be obtained. The entire process takes three to four hours to complete, and multiple samples can be tested simultaneously. The cost for testing each sample ranges from five hundred to seven hundred taka.In this context, contact has been made with the livestock officers of Sreemangal and Rangpur to provide information to UNB about the current situation of livestock blood parasites and disease diagnosis at the field level.
As cancer treatment advances, patients and doctors push back against drugs' harsh side effectsDr. Karna Chandra mallik, Upazila Livestock Officer of Sreemangal Upazila, said that the urine of animals infected with Babesia turns the color of coffee. Although Babesia disease can be diagnosed by examining urine, symptoms of Theileria and Anaplasma cannot be identified by such means.Dr. Md. Zobidul Kabir, Additional District Livestock Officer of Rangpur district, said that the emergence of these three diseases—Babesia, Theileria, and Anaplasma—was not as prevalent in Bangladesh in the past. However, in the current context, these diseases have been prominently observed in highly productive livestock breeds in the Rangpur region. Consequently, the production of dairy and livestock products faces challenges.Livestock officers further stated that Anaplasmosis spreads from one animal to another through tick bites. In advanced countries, if a livestock animal is affected by this disease, it is immediately removed from the farm. However, as this method is not prevalent in our country, the rate of infection in cattle farms is significantly higher.They also added that the Field Disease Investigation Laboratory (FDIL) identifies these diseases through the Giemsa staining from blood sample which need skilled manpower. Often, there is uncertainty in identifying Theileria and Anaplasma, and even the results obtained from samples tested in various private diagnostic centers in Rangpur have been confusing.Dr. Zobidul commended Dr. Shahiduzzaman's success, stating that if the DNA method for identifying livestock diseases could be implemented at the field level, it would play a significant role in the development of livestock.Dr. Shahiduzzaman further remarked that as a veterinarian, it is his professional responsibility to enhance the livestock of the country. If this technology is adopted at the field level with the cooperation of the government as well as respective authorities, it will benefit farmers.
Why don’t we have tails like our ancient animal ancestors? Scientists finally have an answer
Our very ancient animal ancestors had tails. Why don’t we?
Somewhere around 20 million or 25 million years ago, when apes diverged from monkeys, our branch of the tree of life shed its tail. From Darwin’s time, scientists have wondered why — and how — this happened.
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Now, researchers have identified at least one of the key genetic tweaks that led to this change.
“We found a single mutation in a very important gene,” said Bo Xia, a geneticist at the Broad Institute and co-author of a study published Wednesday in the journal Nature.
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The researchers compared the genomes of six species of apes, including humans, and 15 species of monkeys with tails to pinpoint key differences between the groups. Once they identified a significant mutation, they tested their theory by using the gene-editing tool CRISPR to tweak the same spot in mouse embryos. Those mice were born without tails.
Xia cautioned that other genetic changes may also play a role in losing tails.
Another mystery: Did having no tails actually help these ape ancestors -- and eventually, humans — survive? Or was it just a chance mutation in a population that thrived for other reasons?
“It could be random chance, but it could have brought a big evolutionary advantage,” said Miriam Konkel, an evolutionary geneticist at Clemson University, who was not involved in the study.
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As to why having no tails may have helped, there are many tantalizing theories — including some that link being tailless to humans eventually learning to walk upright.
Rick Potts, who directs the Smithsonian Institution’s Human Origins Project and was not involved in the research, suggests being tailless may have been a first step toward some apes adopting a vertical body posture, even before they left the trees.
Not all apes live on the ground today. Orangutans and gibbons are tailless apes that still live in trees. But Potts notes that they move very differently than monkeys, who scamper along the tops of branches, using their tails for balance. Those apes hang below branches, swinging between them while hanging largely upright.
New York University biologist Itai Yanai, a co-author of the study, said that losing our tails was clearly a major transition. But the only way to certainly know the reason “would be to invent a time machine,” he said.
A pacemaker for the brain helped a woman with crippling depression. It may soon offer hope to others
Emily Hollenbeck lived with a deep, recurring depression she likened to a black hole, where gravity felt so strong and her limbs so heavy she could barely move. She knew the illness could kill her. Both of her parents had taken their lives.
She was willing to try something extreme: Having electrodes implanted in her brain as part of an experimental therapy.
Researchers say the treatment —- called deep brain stimulation, or DBS — could eventually help many of the nearly 3 million Americans like her with depression that resists other treatments. It’s approved for conditions such as Parkinson’s disease and epilepsy, and many doctors and patients hope it will become more widely available for depression soon.
The treatment gives patients targeted electrical impulses, much like a pacemaker for the brain. A growing body of recent research is promising, with more underway — although two large studies that showed no advantage to using DBS for depression temporarily halted progress, and some scientists continue to raise concerns.
Meanwhile, the Food and Drug Administration has agreed to speed up its review of Abbott Laboratories’ request to use its DBS devices for treatment-resistant depression.
“At first I was blown away because the concept of it seems so intense. Like, it’s brain surgery. You have wires embedded in your brain,” said Hollenbeck, who is part of ongoing research at Mount Sinai West. “But I also felt like at that point I tried everything, and I was desperate for an answer.”
“NOTHING ELSE WAS WORKING”
Hollenbeck suffered from depression symptoms as a child growing up in poverty and occasional homelessness. But her first major bout happened in college, after her father’s suicide in 2009. Another hit during a Teach for America stint, leaving her almost immobilized and worried she’d lose her classroom job and sink into poverty again. She landed in the hospital.
“I ended up having sort of an on-and-off pattern,” she said. After responding to medication for a while, she’d relapse.
She managed to earn a doctorate in psychology, even after losing her mom in her last year of grad school. But the black hole always returned to pull her in. At times, she said, she thought about ending her life.
She said she’d exhausted all options, including electroconvulsive therapy, when a doctor told her about DBS three years ago.
“Nothing else was working,” she said.
She became one of only a few hundred treated with DBS for depression.
Hollenbeck had the brain surgery while sedated but awake. Dr. Brian Kopell, who directs Mount Sinai’s Center for Neuromodulation, placed thin metal electrodes in a region of her brain called the subcallosal cingulate cortex, which regulates emotional behavior and is involved in feelings of sadness.
The electrodes are connected by an internal wire to a device placed under the skin in her chest, which controls the amount of electrical stimulation and delivers constant low-voltage pulses. Hollenbeck calls it “continous Prozac.”
Doctors say the stimulation helps because electricity speaks the brain’s language. Neurons communicate using electrical and chemical signals.
In normal brains, Kopell said, electrical activity reverberates unimpeded in all areas, in a sort of dance. In depression, the dancers get stuck within the brain’s emotional circuitry. DBS seems to “unstick the circuit,” he said, allowing the brain to do what it normally would.
Hollenbeck said the effect was almost immediate.
“The first day after surgery, she started feeling a lifting of that negative mood, of the heaviness,” said her psychiatrist, Dr. Martijn Figee. “I remember her telling me that she was able to enjoy Vietnamese takeout for the first time in years and really taste the food. She started to decorate her home, which had been completely empty since she moved to New York.”
For Hollenbeck, the most profound change was finding pleasure in music again.
“When I was depressed, I couldn’t listen to music. It sounded and felt like I was listening to radio static,” she said. “Then on a sunny day in the summer, I was walking down the street listening to a song. I just felt this buoyancy, this, ‘Oh, I want to walk more, I want to go and do things!’ And I realized I’m getting better.”
She only wishes the therapy had been there for her parents.
THE TREATMENT’S HISTORY
The road to this treatment stretches back two decades, when neurologist Dr. Helen Mayberg led promising early research.
But setbacks followed. Large studies launched more than a dozen years ago showed no significant difference in response rates for treated and untreated groups. Dr. Katherine Scangos, a psychiatrist at the University of California, San Francisco, also researching DBS and depression, cited a couple of reasons: The treatment wasn’t personalized, and researchers looked at outcomes over a matter of weeks.
Some later research showed depression patients had stable, long-term relief from DBS when observed over years. Overall, across different brain targets, DBS for depression is associated with average response rates of 60%, one 2022 study said.
Treatments being tested by various teams are much more tailored to individuals today. Mount Sinai’s team is one of the most prominent researching DBS for depression in the U.S. There, a neuroimaging expert uses brain images to locate the exact spot for Kopell to place electrodes.
“We have a template, a blueprint of exactly where we’re going to go,” said Mayberg, a pioneer in DBS research and founding director of The Nash Family Center for Advanced Circuit Therapeutics at Mount Sinai. “Everybody’s brain is a little different, just like people’s eyes are a little further apart or a nose is a little bigger or smaller.”
Other research teams also tailor treatment to patients, although their methods are slightly different. Scangos and her colleagues are studying various targets in the brain and delivering stimulation only when needed for severe symptoms. She said the best therapy may end up being a combination of approaches.
As teams keep working, Abbott is launching a big clinical trial this year, ahead of a potential FDA decision.
“The field is advancing quite quickly,” Scangos said. “I’m hoping we will have approval within a short time.”
But some doctors are skeptical, pointing to potential complications such as bleeding, stroke or infection after surgery.
Dr. Stanley Caroff, an emeritus professor of psychiatry at the University of Pennsylvania, said scientists still don’t know the exact pathways or mechanisms in the brain that produce depression, which is why it’s hard to pick a site to stimulate. It’s also tough to select the right patients for DBS, he said, and approved, successful treatments for depression are available.
“I believe from a psychiatric point of view, the science is not there,” he said of DBS for depression.
MOVING FORWARDHollenbeck acknowledges DBS hasn’t been a cure-all; she still takes medicines for depression and needs ongoing care.
She recently visited Mayberg in her office and discussed recovery. “It’s not about being happy all the time,” the doctor told her. “It’s about making progress.”
That’s what researchers are studying now — how to track progress.
Recent research by Mayberg and others in the journal Nature showed it’s possible to provide a “readout” of how someone is doing at any given time. Analyzing the brain activity of DBS patients, researchers found a unique pattern that reflects the recovery process. This gives them an objective way to observe how people get better and distinguish between impending depression and typical mood fluctuations.
Scientists are confirming those findings using newer DBS devices in a group of patients that includes Hollenbeck.
She and other participants do their part largely at home. She gives researchers regular brain recordings by logging onto a tablet, putting a remote above the pacemaker-like device in her chest and sending the data. She answers questions that pop up about how she feels. Then she records a video that will be analyzed for things such as facial expression and speech.
Occasionally, she goes into Mount Sinai’s “Q-Lab,” an immersive environment where scientists do quantitative research collecting all sorts of data, including how she moves in a virtual forest or makes circles in the air with her arms. Like many other patients, she moves her arms faster now that she’s doing better.
Data from recordings and visits are combined with other information, such as life events, to chart how she’s doing. This helps guide doctors’ decisions, such as whether to increase her dose of electricity – which they did once.
On a recent morning, Hollenback moved her collar and brushed her hair aside to reveal scars on her chest and head from her DBS surgery. To her, they’re signs of how far she’s come.
She makes her way around the city, taking walks in the park and going to libraries, which were a refuge in childhood. She no longer worries that normal life challenges will trigger a crushing depression.
“The stress is pretty extreme at times, but I’m able to see and remember, even on a bodily level, that I’m going to be OK,” she said.
“If I hadn’t had DBS, I’m pretty sure I would not be alive today.”
Japan space agency says test flight for new flagship rocket is rescheduled for Saturday
Japan’s space agency says its new flagship H3 rocket will have a second test flight on Saturday, two days later than an initially planned liftoff that was postponed due to a bad weather forecast at the launch site in southwestern Japan.
The liftoff was originally scheduled for Thursday but was postponed due to thunder and strong wind forecasted at the Tanegashima Space Center.
The Japan Aerospace Exploration Agency, or JAXA, said Wednesday that its H3 rocket will attempt a test flight on Saturday with an alternative launch window through the end of March.
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JAXA has been developing H3 for more than a decade as a successor to its current mainstay, H-2A, which has just two more flights planned before its retirement.
The upcoming launch is being closely watched as a test for Japan's space development after H3 failed in its debut flight last March, when the rocket had to be destroyed along with its payload, the advanced land observation satellite, or ALOS-3. This time, the rocket will carry a mockup of the ALOS satellite, called VEP-4.
JAXA says the mission's primary goal for the second test flight is to put the rocket into the intended trajectory. The agency also wants to place two observation microsatellites into orbit.
H3 is designed to carry larger payloads than H-2A at much lower costs to be globally competitive.
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Expectations are high following a recent steak of successes. JAXA made a historic precision moon landing last month of its spacecraft that had been launched from the H-2A rocket, days after the 48th H-2A rocket successfully placed a spy satellite into its planned orbit.
China Focus: China employs sci-tech to improve biological breeding, seed varieties
China has boosted its biological breeding industry through scientific and technological methods, contributing greatly to the country's steady supply of grain and other major agricultural products.
In recent years, China has solidly pushed forward its seed industry revitalization, and has achieved a number of breakthroughs.
China has independently bred three new white-feather broiler chicken varieties, thereby ending its previous complete dependence on imports, according to the latest statistics from the Ministry of Agriculture and Rural Affairs and the Chinese Academy of Agricultural Sciences. The market share of these new varieties reached 25.1 percent in 2023 and they were exported abroad for the first time last year.
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China last year also successfully cultivated a new oilseed rape variety with a growth period of only about 169 days. This short growth cycle enables farmers to fully utilize the winter fallow fields in southern China by planting oilseed rape without delaying the planting of early season rice the following year.
In addition, China has managed to establish an independent and complete bio-breeding research and development system, and has secured independent intellectual property rights and core technologies concerning important genes and genetic features, such as insect resistance, herbicide tolerance, drought resistance, salt tolerance, and improved nutritional quality.
Recently, the country's 37 genetically modified corn varieties and 14 genetically modified soybean varieties passed preliminary examinations, according to the ministry. This marked a pioneering step for the industrialization of bio-breeding.
These genetically modified crops showed both outstanding herbicide-tolerant and insect-resistant traits. They could also see a 10 percent rise in yields, demonstrating great development potential.
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As the "chips" of agriculture, seeds are crucial to the development of the industry. Accelerating the promotion and application of transgenic technology is an inevitable choice for increasing future international competitiveness and optimizing industrial division, and is also a key way to ensure the country's food security and boost the sustainable development of agricultural science and technology.
The contribution rate of improved varieties to the increase in grain yield currently exceeds 45 percent, according to official statistics. As a core focus area for the development of the seed industry, sci-tech innovation will help improve China's agricultural sci-tech level and narrow the production capacity gap between China and some leading foreign countries.
"The core goals in the future are to increase production and improve the quality of seeds, reduce the use of chemical fertilizers and pesticides, and decrease losses caused by natural disasters," said Li Jiayang, an academician of the Chinese Academy of Sciences.
Internet users in Bangladesh reach 131 mln as of 2023
The number of internet subscribers reached 131 million at the end of December, 2023, including nearly 7 million new users in the last year, showed the recently released data by the country's telecom regulator.
The Bangladesh Telecommunication Regulatory Commission (BTRC) data showed that of the internet subscribers, some 118.49 million are mobile internet users and 12.88 million broadband internet users.
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Meanwhile, with 10.61 million new mobile users in 2023, the number of subscribers in the country reached 190.81 million in December 2023.
Bangladesh has currently four mobile companies in operation, three of them being foreign-backed cellphone operators.
The number of subscribers of mobile operators Grameen Phone, Robi Axiata, Banglalink Digital Communications and Teletalk Bangladesh stood at 82.20 million, 58.67 million, 43.48 million and 6.46 million, respectively, at the end of December, the data shows.
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Astronauts from Turkey, Italy and Sweden return to Earth, ending private space station trip
Astronauts from Turkey, Italy and Sweden returned to Earth on Friday, ending a private three-week mission to the International Space Station.
The trio were accompanied by a retired NASA astronaut who now works for Axiom Space, the Houston company that arranged the chartered flight. The crew returned in a SpaceX capsule that parachuted into the Atlantic off the Florida coast.
Turkey celebrated Alper Gezeravci’s launch from Cape Canaveral last month. A former fighter pilot and captain for Turkish Airlines, he became the first person from his country to fly in space.
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Gezeravci was joined on the trip by Italian Air Force Col. Walter Villadei, Sweden’s Marcus Wandt, a former fighter pilot chosen as a reserve astronaut by the European Space Agency in 2022 and Michael Lopez-Alegria, their escort.
Turkey, Italy and Sweden financed the mission, paying roughly $55 million apiece. It was Axiom’s third private mission to the space station; the fourth is planned later this year.
Before leaving the space station, Gezeravci thanked his country for its “bold and determined decision” to send a citizen into space as part of its 100th anniversary as a republic.
While in orbit, the astronauts conducted science experiments and chatted with schoolchildren and officials from their countries. They enjoyed a few extra days at the space station, waiting for the weather to improve in the splashdown zone.
Fatty acids play crucial role in memory formation: study
A team led by researchers from the University of Queensland (UQ) has recently shed new light on the crucial role of saturated free fatty acids (FFAs) in the brain's memory creation process.
"We've shown previously that levels of saturated fatty acids increase in the brain during neuronal communication, but we didn't know what was causing these changes," Isaac Akefe, lead author of the study and research fellow at UQ, said on Tuesday.
"Now for the first time, we've identified alterations in the brain's fatty acid landscape when the neurons encode a memory," the scholar noted.
In their latest paper published in EMBO Journal, researchers dived deep into a novel interaction between the Phospholipase A1 (PLA1) isoform DDHD2 and a key synaptic protein dubbed STXBP1 by conducting longitudinal experiments on mice.
They found that STXBP1 controls the targeting of DDHD2 to the plasma membrane and the subsequent generation of saturated FFAs.
"To determine the importance of free fatty acids in memory formation, we used mouse models where the PLA1 gene is removed," said Frederic Meunier, co-author of the study and professor at UQ.
"Even before their memories became impaired, their saturated free fatty acid levels were significantly lower than control mice. This indicates that this PLA1 enzyme, and the fatty acids it releases, play a key role in memory acquisition," he noted.
As the fattiest organ in the body, 60 percent of the human brain consists of lipids, while fatty acids serve as the building blocks of those lipids or fats and are instrumental in communication between nerve cells.
Meunier believed that manipulating this new memory acquisition pathway has "exciting potential" as a treatment for neurodegenerative disorders, such as Alzheimer's disease.
As cancer treatment advances, patients and doctors push back against drugs' harsh side effects
For cancer patients, the harsh side effects of powerful drugs have long been the trade-off for living longer. Now, patients and doctors are questioning whether all that suffering is necessary.
They’ve ignited a movement to radically change how new cancer drugs are tested, with the U.S. Food and Drug Administration urging drugmakers to do a better job at finding the lowest effective dose, even if it takes more time.
Advances in treatment mean millions of people are surviving for years with incurable cancers. Jill Feldman, 54, of Deerfield, Illinois, has lived 15 years with lung cancer, thanks to that progress. Her parents both died of lung cancer months after their diagnoses.
But her cancer drug causes joint pain, fatigue and mouth sores that make eating and drinking painful.
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“If you drink something that’s too hot, you really burn your mouth. That’s how my mouth feels 24/7,” Feldman said.
She has lowered the dose with her doctor’s blessing but she wants drugmakers to study lower doses early in the research process.
“No one should have to endure avoidable harmful effects of treatment,” she said.
Unlike in other diseases, cancer drug development has focused on finding what’s called the “maximum tolerated dose.”
To speed testing of chemotherapy drugs, researchers ramp up the dosage in a few people in early studies to determine the highest possible dose patients can tolerate. That “more is better” philosophy works for chemotherapy, but not necessarily for newer cancer drugs — like the one Feldman takes — which are more targeted and work differently.
Chemotherapy is like a battering ram where aggressive strikes are a good strategy. But newer cancer drugs are more like having a front door key. They target a mutation that drives cancer cell growth, for example, or rev up the body’s immune system to join the fight.
“You might only need a low dose to turn off that cancer driver,” said Dr. Lillian Siu, who leads cancer drug development at the Princess Margaret Cancer Center in Toronto. “If you can get the same bang for your buck, why go higher?”
Through a program called Project Optimus, the FDA is pushing drugmakers to include more patients in early dose-finding trials to get better data on when lower doses can work. A key motivation for the project was "the growing calls from patients and advocates that cancer drugs be more tolerable,” said FDA spokesperson Chanapa Tantibanchachai in an email.
Many of the new cancers drugs were developed using the old strategy. That leads to problems when patients skip doses or stop taking the drugs because of side effects. Some dose recommendations have been officially lowered after the drugs were approved. Other dose-lowering happens one patient at a time. Nearly half of patients in late-stage trials of 28 targeted therapy drugs needed to have their doses lowered, according to one study.
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“We were pushing the dose as high as we could go,” said Dr. Patricia LoRusso, who leads drug discovery at Yale School of Medicine. “You get side effects and then you have to stop the drug to recover from the side effects and the tumor can grow.”
There's also huge patient-to-patient variation. The amount of a pill that reaches the bloodstream can vary because of liver and kidney function and other differences. But that means lowering the dose for everyone risks underdosing some patients, LoRusso said.
“The challenge is: Where is the sweet spot?” LoRusso said.
Dr. Julie Gralow, chief medical officer of the American Society of Clinical Oncology, is planning a 500-patient study to test whether lower doses of two drugs for breast cancer that has spread.
The study will compare two strategies: Starting treatment at the full dose then lowering the dose for side effects versus starting with a lower dose and increasing dosage if the patient does well.
Much of the questioning of high doses has come from metastatic breast cancer patients, including the Patient Centered Dosing Initiative, which has done influential surveys of patients and cancer doctors.
“We will be on treatment for the rest of our lives,” said Lesley Kailani Glenn, 58, of Central Point, Oregon. “We want to try to live the best that we can, knowing that treatment is never-ever going to stop.”
During the 11 years she's lived with the disease, she has summited Mount Whitney in California, hiked the Cinque Terra in Italy and started a nonprofit.
When Glenn learned how cancer drug research favors high doses, she started working with her doctor. She has taken drugs at lower doses and even lower when she can’t live with the side effects. Diarrhea is her deal-breaker: She wants to be able to walk her dog or shop for groceries without worrying about a bathroom emergency.
“The last thing we want to do is have our quality of life stolen from us,” Glenn said.
Through Project Optimus, the FDA is encouraging drug developers to conduct more head-to-head dosing comparisons. That could slow down the process, said Dr. Alice Shaw, who leads early cancer drug development at Novartis.
“That will require more patients and then, as you can imagine, also will require more time to identify, enroll and treat those patients,” said Shaw said. Adding six months to a year to the process, Shaw said, needs to be balanced against the urgent need for new cancer drugs.
But getting the dose right early will in the long run lead to more effective drugs, said Dr. Timothy Yap, a drug developer at MD Anderson Cancer Center in Houston. “If the patients are not taking the drug, then it’s not going to work.”