Moffitt study reveals new mechanism of drug resistance in melanoma leptomeningeal disease
Findings uncover key tumor-stroma interactions and a potential therapeutic target
2024-06-11
(Press-News.org) TAMPA, Fla. — Leptomeningeal disease is a rare but lethal complication faced by late-stage melanoma patients. It occurs when cancer cells spread to the membranes covering the brain and spinal cord, or the leptomeninges. This condition, which affects 5% to 8% of melanoma patients, often leads to rapid deterioration and is notoriously resistant to therapies. However, a new Moffitt Cancer Center study, published today in Cell Reports Medicine, uncovers the mechanisms that drive this drug resistance, offering new avenues for potential treatments.
Moffitt researchers analyzed tissue specimens from patients with leptomeningeal disease and compared them with metastases from other body parts in the same individuals. They found that melanoma cells in the leptomeninges interact significantly with stromal cells. Under healthy conditions, stromal cells play crucial roles in maintaining the health and function of various tissues and organs in the body. In melanoma leptomeningeal metastasis, the interactions between these stromal cells and the tumor activate tumor-promoting signals.
“Understanding the unique environment of leptomeningeal metastasis in melanoma has been a major challenge. Our findings demonstrate that the ‘normal’ stromal cells in the leptomeninges play a crucial role in supporting tumor growth and resistance to MAPK inhibitors, a common melanoma treatment,” said Inna Smalley, Ph.D., senior author, assistant member of the Department of Metabolism and Physiology and a member of the Donald A. Adam Melanoma and Skin Cancer Center of Excellence.
The researchers’ cutting-edge spatial transcriptomics analysis uncovered spatially driven signaling pathways associated with melanoma growth and drug resistance, particularly in regions where tumor and stromal cells interact. They identified the protein SERPINA3 as a regulator of the tumor-stroma interactions, suggesting a potential target for therapeutic intervention.
“Our data suggest that targeting the tumor-stroma interaction, particularly through inhibition of SERPINA3-mediated signaling, could represent a novel strategy to overcome drug resistance in melanoma leptomeningeal disease,” Smalley said. “By disrupting this critical interaction, we may be able to enhance the efficacy of existing therapies and improve patient outcomes.”
The study also highlighted melanoma cells’ unique metabolic challenges in the cerebrospinal fluid. The team demonstrated that the meningeal stroma is essential for melanoma cells’ survival in this harsh environment, further underscoring the importance of the tumor-stroma interaction.
Their work was supported by the Melanoma Research Alliance (932727), the American Cancer Society (RSG-23-1040487-01-MM), and the National Institutes of Health (T32CA23339, R00 CA226679, R21 CA274060, P30-CA076292).
About Moffitt Cancer Center
Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 57 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt’s scientific excellence, multidisciplinary research, and robust training and education. Moffitt’s expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet® status, its highest distinction. For more information, call 1-888-MOFFITT (1-888-663-3488), visit MOFFITT.org, and follow the momentum on Facebook, Twitter, Instagram and YouTube.
###
END
ELSE PRESS RELEASES FROM THIS DATE:
2024-06-11
Iran’s water policy is discriminatory and an example of environmental racism, with specific regions and ethnic groups deliberately impoverished, damaged and threatened by policymakers, a new study says.
Water scarcity lies at the core of Iran’s environmental crises. Approximately 28 million of Iran’s 85 million residents reside in water-stressed areas, a situation identified as ‘water bankruptcy’. This is particularly the case in the central, industrialised regions.
Other “donor basin” regions – which have ...
2024-06-11
The 2024 Warren Alpert Foundation Prize has been awarded to four scientists whose transformational discoveries led to the creation of chimeric antigen receptor (CAR) T cells, a treatment that modifies patients’ immune cells and optimizes their ability to eliminate cancer cells.
CAR T-cell therapy, the first successful example of synthetic biology used in clinical medicine, has saved the lives of tens of thousands of adults and children with blood cancers, including leukemia, lymphoma, and multiple myeloma.
The award recipients are:
Renier Brentjens, Katherine Anne Gioia Endowed Chair of Medicine and deputy director of Roswell Park Comprehensive Cancer Center
Zelig ...
2024-06-11
Metabolic syndrome (MetS) is a health condition characterized by a group of risk factors: high blood pressure, high blood sugar, unhealthy cholesterol levels, and abdominal fat. These factors increase the risk of heart disease, type 2 diabetes, and other serious health problems.
Previous studies have shown that both genetics and lifestyle influence MetS. But human studies have found it challenging to pinpointing the disease’s exact genetic factors and how they interact with our environment – the differences between people’s diets and lifestyles have proven impossible to control.
Now, scientists led by Johan Auwerx at EPFL have addressed ...
2024-06-11
WhatsApp can be a highly effective tool to help older people overcome loneliness and depression, according to the findings of a study conducted in Guarulhos, the second-largest city in São Paulo state, Brazil.
An article on the study is published in the journal Nature Medicine. The co-corresponding author is Marcia Scazufca, a scientific researcher at Hospital das Clínicas (HC), the hospital complex run by the University of São Paulo’s Medical School (FM-USP), and a professor at the school.
“This was a randomized controlled trial involving 603 participants aged more than 60 and registered ...
2024-06-11
The ocean, rich in mineral resources such as oil, natural gas, polymetallic nodules, cobalt-rich ferromanganese crusts, polymetallic sulfides, and rare earth ore, plays an increasingly important role in resource development and economic growth. It is also regarded as an essential strategic space for sustainable development with abundant wind, wave, tidal, and solar energy. Compared with onshore structures, however, offshore structures, being complex, bulky, and expensive, have to endure various random loads that change over time and space, including wind, waves, currents, tides, sea ice, and even coupled with ...
2024-06-11
When college athletes are evaluated for a possible concussion, the diagnosis is based on an athletic trainer or team physician’s assessment of three things: the player’s symptoms, physical balance and cognitive skills.
Research published today suggests that almost half of athletes who are ultimately diagnosed with a concussion will test normally on the recommended cognitive-skills test.
“If you don’t do well on the cognitive exam, it suggests you have a concussion. But many people who are concussed do fine on the exam,” said Dr. Kimberly Harmon, the study’s lead author. She is a professor of family medicine ...
2024-06-11
As long as humans have been traveling into space, astronauts have experienced significant health effects from the extreme conditions of space flight, notably the reduction of gravity.
Two Buck scientists led a team that has revealed for the first time how the lack of gravity affects the cells of the immune system at single cell resolution. As co-senior authors, along with Christopher E. Mason, PhD of Weill Cornell Medical College, Associate Professor David Furman, PhD and Associate Professor Daniel Winer, MD, published in the ...
2024-06-11
Food insecurity, low household income and not having private health insurance are associated with higher rates of prediabetes in adolescents, independent of race and ethnicity, according to a new JAMA Network Open study by University of Pittsburgh and UPMC researchers.
The findings suggest that screening for social determinants of health — the non-medical factors that influence a person's health and risk of disease — may help identify youth at risk of prediabetes, which could ultimately improve early interventions that prevent progression to type 2 diabetes.
“This study underscores the importance ...
2024-06-11
The agility with which humans and animals move is an evolutionary marvel that no robot has yet been able to closely emulate. To help probe the mystery of how brains control movement, Harvard neuroscientists have created a virtual rat with an artificial brain that can move around just like a real rodent.
Bence Ölveczky, professor in the Department of Organismic and Evolutionary Biology, led a group of researchers who collaborated with scientists at Google’s DeepMind AI lab to build a biomechanically realistic digital model of a rat. Using high-resolution data recorded from ...
2024-06-11
Scientists unlock secrets of how the third form of life makes energy.
An international scientific team has redefined our understanding of archaea, a microbial ancestor to humans from two billion years ago, by showing how they use hydrogen gas.
The findings, published today in Cell, explain how these tiny lifeforms make energy by consuming and producing hydrogen. This simple but dependable strategy has allowed them to thrive in some of Earth’s most hostile environments for billions of years.
The paper, led by Monash University Biomedicine Discovery Institute scientists, including ...
LAST 30 PRESS RELEASES:
[Press-News.org] Moffitt study reveals new mechanism of drug resistance in melanoma leptomeningeal disease
Findings uncover key tumor-stroma interactions and a potential therapeutic target
