(Press-News.org) For some leukemia patients, the only potential chemotherapy option is a drug that also carries a high risk of heart failure. This means that some patients who recover from their cancer will end up dying of heart disease brought on by the cure.
In a new study, researchers from the University of Illinois Chicago and other universities have identified mechanisms that cause the drug, ponatinib, to harm the heart. They also identified a promising treatment that could reverse this process. The paper, with senior author Sang Ging Ong, assistant professor of pharmacology and medicine at UIC, is published in Circulation Research. The study is part of a growing field called cardio-oncology that investigates drugs that shrink tumors but can also cause heart problems.
While there are three options of drugs for treating chronic myeloid leukemia, many patients are resistant to the other two, leaving ponatinib as their only choice.
“These patients have no other options for treatment,” Ong said, despite the concerns about the drug’s side effects. In fact, ponatinib was pulled from the market for a few months after its introduction in 2012 because of concerns about heart problems.
The researchers were interested in understanding the interaction between ponatinib and the heart cells responsible for contraction. They discovered that ponatinib damages these cells by activating a process known as the integrated stress response.
The mechanism for this is related to the functioning of a kinase — an enzyme involved in energy transfer — called GCN2. The researchers found that ponatinib, despite being a kinase inhibitor, actually activates GCN2, which in turn switches on the integrated stress response. While this response isn’t always a bad thing — its purpose is to protect cells — it can also lead to their death under prolonged stress.
To see if this response was harming the cells, the researchers studied what would happen if they used a small molecule to block the integrated stress response in both cells and in mice during ponatinib treatment. They found that the treatment helped protect heart cells from the damaging side effects of the drug yet did not diminish ponatinib’s tumor-fighting efficacy.
“It protects the heart but at the same time, it still allows us to kill cancer cells,” Ong said.
More research is needed to know if this protective measure would work well in humans, Ong said. The mechanisms they identified are important in other cardiac diseases, as well, which could lead to future research on how to protect cells against different conditions.
Ong’s co-senior authors on the study are Won Hee Lee at the University of Arizona and Sang-Bing Ong at the Chinese University of Hong Kong. Other UIC authors at the College of Medicine or University of Illinois Cancer Center are Gege Yan, Zhenbo Han, Youjeong Kwon, Jordan Jousma, Sarath Babu Nukala, Xiaoping Du and Sandra Pinho, as well as Benjamin Prosser from the University of Pennsylvania.
Written by Emily Stone
Clues to cancer drug’s deadly side effects could make it safer
ELSE PRESS RELEASES FROM THIS DATE:
Surprise discovery of tiny insect-killing worm
UC Riverside scientists have discovered a tiny worm species that infects and kills insects. These worms, called nematodes, could control crop pests in warm, humid places where other beneficial nematodes are currently unable to thrive. This new species is a member of a family of nematodes called Steinernema that have long been used in agriculture to control insect parasites without pesticides. Steinernema are not harmful to humans or other mammals and were first discovered in the 1920s. “We spray trillions of them on crops every year, and they’re ...
Are environmental toxins putting future generations at risk?
In a study that signals potential reproductive and health complications in humans, now and for future generations, researchers from McGill University, the University of Pretoria, Université Laval, Aarhus University, and the University of Copenhagen, have concluded that fathers exposed to environmental toxins, notably DDT, may produce sperm with health consequences for their children. The decade-long research project examined the impact of DDT on the sperm epigenome of South African Vhavenda and Greenlandic ...
Protecting the protector boosts plant oil content
UPTON, NY—Biologists at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory have demonstrated a new way to boost the oil content of plant leaves and seeds. As described in the journal New Phytologist, the scientists identified and successfully altered key portions of a protein that protects newly synthesized oil droplets. The genetic alterations essentially protect the oil-protector protein so more oil can accumulate. “Implementing this strategy in bioenergy or oil crop plants could ...
Physical activity is insufficient to counter cardiovascular risk associated with sugar-sweetened beverage consumption
Québec, February 8, 2024 - Contrary to popular belief, the benefits of physical activity do not outweigh the risks of cardiovascular disease associated with drinking sugar-sweetened beverages, according to a new study led by Harvard T. H. Chan School of Public Health. Jean-Philippe Drouin-Chartier, professor at Université Laval’s Faculty of Pharmacy, was a co-author. Sugar-sweetened beverages are the largest source of added sugars in the North American diet. Their consumption is associated with ...
CARB-X funds Visby Medical to develop a portable rapid diagnostic for gonorrhea including antibiotic susceptibility
(BOSTON: Thursday, February 8, 2024) – Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) will award up to US$1.8 million to biotechnology company, Visby Medical, to develop a portable rapid polymerase chain reaction (PCR) diagnostic to detect the presence of the pathogen that causes gonorrhea, Neisseria gonorrhoeae (NG), and its susceptibility to ciprofloxacin, a former frontline oral antibiotic that can no longer treat resistant NG. A rapid result on when ciprofloxacin may be effective could enable physicians to treat gonorrhea patients with confidence, while reserving ceftriaxone, the only antibiotic that remains effective against resistant NG. Visby ...
Fusion research facility JET’s final tritium experiments yield new energy record
GARCHING and OXFORD (8 February 2024) – The Joint European Torus (JET), one of the world’s largest and most powerful fusion machines, has demonstrated the ability to reliably generate fusion energy, whilst simultaneously setting a world-record in energy output. These notable accomplishments represent a significant milestone in the field of fusion science and engineering. In JET's final deuterium-tritium experiments (DTE3), high fusion power was consistently produced for 5 seconds, resulting in a ground-breaking record of 69 megajoules using a mere 0.2 milligrams of fuel. JET is a tokamak, a design which uses powerful ...
A new “metal swap” method for creating lateral heterostructures of 2D materials
Electronically conducting two-dimensional (2D) materials are currently hot topics of research in both physics and chemistry owing to their unique properties that have the potential to open up new avenues in science and technology. Moreover, the combination of different 2D materials, called heterostructures, expands the diversity of their electrical, photochemical, and magnetic properties. This can lead to innovative electronic devices not achievable with a single material alone. Heterostructures can be fabricated in two ways: vertically, with materials ...
Study visually captures a hard truth: Walking home at night is not the same for women
An eye-catching new study shows just how different the experience of walking home at night is for women versus men. The study, led by Brigham Young University public health professor Robbie Chaney, provides clear visual evidence of the constant environmental scanning women conduct as they walk in the dark, a safety consideration the study shows is unique to their experience. Chaney and co-authors Alyssa Baer and Ida Tovar showed pictures of campus areas at four Utah universities — Utah Valley University, ...
Ice cores provide first documentation of rapid Antarctic ice loss in the past
Researchers from the University of Cambridge and the British Antarctic Survey have uncovered the first direct evidence that the West Antarctic Ice Sheet shrunk suddenly and dramatically at the end of the Last Ice Age, around eight thousand years ago. The evidence, contained within an ice core, shows that in one location the ice sheet thinned by 450 metres — that’s more than the height of the Empire State Building — in just under 200 years. This is the first evidence anywhere in Antarctica for such a fast loss of ice. Scientists are worried that today’s rising temperatures ...
Faulty DNA disposal system causes inflammation
LA JOLLA (February 8, 2024)—Cells in the human body contain power-generating mitochondria, each with their own mtDNA—a unique set of genetic instructions entirely separate from the cell’s nuclear DNA that mitochondria use to create life-giving energy. When mtDNA remains where it belongs (inside of mitochondria), it sustains both mitochondrial and cellular health—but when it goes where it doesn’t belong, it can initiate an immune response that promotes inflammation. Now, Salk scientists ...