MD Anderson research highlights for September 4, 2024

Featuring markers of immunotherapy response, spatial biology advances, new epigenetic targets and novel treatment approaches

2024-09-04

(Press-News.org) HOUSTON ― The University of Texas MD Anderson Cancer Center’s Research Highlights showcases the latest breakthroughs in cancer care, research and prevention. These advances are made possible through seamless collaboration between MD Anderson’s world-leading clinicians and scientists, bringing discoveries from the lab to the clinic and back.

Protein expression atlas covers almost all cancer hallmarks
The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) provide DNA and RNA data from approximately 11,000 patient samples across 33 cancer types and 1,000 cancer cell lines, but limited protein information is available. Researchers led by Han Liang, Ph.D., Rehan Akbani, Ph.D., and Jun Li, Ph.D., previously generated protein expression data for approximately 200 proteins but did not include many cancer-related pathways. In a new study, the researchers characterized expression of nearly 500 proteins, using 8,000 TCGA samples and 900 CCLE samples. These results cover almost all known cancer hallmarks and targets, and the findings identified interactions and meaningful patterns among proteins with potential translational impact. This atlas highlights the value of considering protein expression as part of an integrated research approach to aid future diagnostic and treatment strategies for patients with cancer and other diseases. Learn more in Nature Cancer.

Immunological features predict treatment response for advanced solid tumors
Immune checkpoint therapy stimulates tumor infiltration by CD8 T cells to facilitate an antitumor response, but many advanced solid tumors do not respond to treatment. In the AMADEUS trial, researchers led by Padmanee Sharma, M.D., Ph.D., aimed to identify biomarkers that predict treatment response in patients with advanced solid tumors. The trial enrolled 39 patients who were divided into two groups based on pre-treatment levels of CD8 T cells. Those with low CD8 levels received a combination of nivolumab plus ipilimumab, while those with high CD8 levels received nivolumab alone. The disease control rate for low-CD8 and high-CD8 patients was 25% and 14.3%, respectively, and 39.5% of tumors that initially were low-CD8 had an influx of CD8 T cells after treatment. Treatment improved the inflammatory tumor microenvironment in low-CD8 responders, leading to better outcomes. These results provide insights into more efficient ways to stratify patients using immunological features to personalize treatment. Learn more in the Journal of Experimental Medicine.

Novel targets overcome treatment resistance in triple-negative breast cancer
Patients with triple-negative breast cancer (TNBC), an aggressive subtype, currently have limited options and generally face a poor prognosis. Researchers led by Khandan Keyomarsi, Ph.D., Li Mi, Ph.D., and Amriti Lulla, Ph.D., discovered that increased levels of low molecular weight cyclin-E (LMW-E) and cyclin-dependent kinase (CDK1) phosphorylation are associated with poor outcomes following chemotherapy. High levels of LMW-E and CDK1 predicted the poorest treatment responses, suggesting they serve as potential biomarkers of chemotherapy resistance. The study showed that LMW-E upregulates and stabilizes PKMYT1, leading to enhanced CDK1 phosphorylation. TNBC cells with high LMW-E levels were more sensitive to the PKMYT1 inhibitor RP-6306, which induces DNA damage and mitotic arrest. Treatment with RP-6306 also led to tumor suppression, increased DNA damage and extended survival in vivo, using both patient derived xenograft and transgenic models. These findings highlight the therapeutic potential of PKMYT1 inhibitors for patients with TNBC. Learn more in Cancer Research.

New spatial profiling tool provides detailed molecular insights into cancer cells and the tumor microenvironmentSpatial transcriptomics techniques provide information on the location of gene expression patterns, uncovering cell organization and interactions within specific areas of the tumor microenvironment (TME). However, many analytical tools don’t take cell morphology or tissue histology into consideration. To improve these methods, researchers led by Linghua Wang, M.D., Ph.D., and Jiahui Jiang, Ph.D., developed the Morphology-Enhanced Spatial Transcriptome Analysis Integrator (METI). This tool integrates histology, spatial transcriptomics and domain knowledge of cancer genomics to map cancer cells and their microenvironment components, to stratify different cell types and states, and to analyze areas where cells interact within the TME. After testing METI on various tumor tissues from gastric, lung and bladder cancers, as well as premalignant tissues, the researchers found that this tool provides more accurate and detailed insights into the TME than existing methods. This highlights its potential to advance our understanding of tumor biology and to aid in the development of diagnostic and therapeutic strategies. Learn more in Nature Communications.

Epigenetic target drives multiple myeloma development
Multiple myeloma is a rare blood cancer that originates in bone marrow and has limited treatment options. Studies have shown that the SAGA complex – a histone acetyltransferase and transcriptional co-activator – is linked to disease progression, but how it contributes to cancer development is not well understood. To provide insights, researchers led by Ying-Jiun Chen, Ph.D., and Sharon Dent, Ph.D., examined the effects of losing ADA2B, a unique subunit of the SAGA complex, in multiple myeloma. They found ADA2B is essential for activating pathways and gene targets of the MAF and MYC transcription factors, which drive multiple myeloma survival and progression. The researchers also identified a specific domain of ADA2B that is necessary for its stability and interaction with SAGA, highlighting its potential as a therapeutic target for patients with multiple myeloma and other diseases. Learn more in Genes & Development.

Scientists identify new epigenetic target for chromosomal instability in ICF syndrome
Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is a rare genetic disorder linked to the hypomethylation of certain chromosomal areas containing repetitive DNA sequences. These repetitive sequences are prone to forming DNA structures that are different from the predominant B-DNA configuration during replication, which can sometimes cause genomic instability. The CDCA7 protein is mutated in ICF syndrome, but its role in DNA methylation in these chromosomal regions is unknown. Researchers led by Taiping Chen, Ph.D., and Xiaodong Cheng, Ph.D., found that CDCA7 has a specific domain that normally binds non-B-DNA regions during cell replication, concentrating in these particular chromosomal areas and ensuring proper DNA methylation and stability. CDCA7 mutations in ICF syndrome disrupt that ability, which explains the loss of methylation in these regions. Understanding how CDCA7 and its mutants interact with DNA may help in developing therapeutic strategies for ICF syndrome and related disorders. Learn more in Science Advances.

New approach to treating lung fibrosis shows early promise in two preclinical models
Idiopathic pulmonary fibrosis (IPF), a disease that causes lung scarring, is associated with a low life expectancy and few treatment options. As such, it is a major cause of death. Currently, lung transplantation is the only effective treatment, but many patients are unable to receive an organ donation due to a shortage of suitable lungs and a high risk of mortality from the transplant procedure. To examine alternative options, researchers led by Yair Reisner, Ph.D., evaluated a lung stem cell transplant, using single-cell suspensions of an entire lung, in two distinct in vivo models of lung fibrosis. The transplant successfully attenuated disease progression, resulting in improved lung function and a reduction of fibrotic tissue compared to untreated controls. The study offers proof-of-concept for further investigation into the treatment of lung fibrosis using lung cell suspensions via intravenous infusions for patients with IPF and chemotherapy-induced lung injury. Learn more in Science Advances.

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Americans face disparities in exposure to tobacco on streaming platforms MD Anderson receives over $21.4 million in CPRIT funding to support research and launch new core facilities Read this press release in the MD Anderson Newsroom.

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At-risk butterflies more likely to survive with human help

2024-09-04

VANCOUVER, Wash. – Some of the butterflies most in danger of fluttering out of existence fare better when their habitats are actively managed by humans, a recent study found. A team led by Washington State University researchers Cheryl Schultz and Collin Edwards analyzed data on 114 populations of 31 butterfly species in 10 U.S. states. Scientists have long warned that insect populations worldwide are falling rapidly due to the combined effects of climate change, habitat loss and pesticides. Overall, the research team found that these at-risk butterflies ...

National Cleveland Clinic survey examines generational divide in men's health

2024-09-04

Embargoed until 12:01 a.m. Wednesday, September 4, 2024, CLEVELAND: A new national survey by Cleveland Clinic revealed similarities and differences across generations when it comes to men’s health. The survey highlights health priorities and concerns among men; however, there were generational differences in health habits, mental health and the use of social media as a source of health information. While 95% of men surveyed said living a healthy lifestyle is their top priority, findings show that different health behaviors exist among ...

Sex and size disparities in access to liver transplant for patients with hepatocellular carcinoma

2024-09-04

About The Study: In this study, women with hepatocellular carcinoma were less likely to receive a deceased-donor liver transplant and more likely to die while wait-listed than men with hepatocellular carcinoma; these differences were largely (but not entirely) explained by sex-based differences in candidate size. For candidates listed with exception scores, additional changes to allocation policy are needed to resolve the sex disparity, including solutions to improve access to size-matched donor livers for smaller candidates. Corresponding Author: To ...

The world's first nuclear clock

2024-09-04

For many years, scientists all around the world have been working towards this goal, now suddenly things are happening very fast: it was only in April that a team led by Prof Thorsten Schumm (TU Wien, Vienna) announced a major success. For the first time, an atomic nucleus had been switched from one state to another using a laser – an effect that can be used for high-precision measurements. Now, just a few weeks later, this thorium transition was successfully applied in practice: TU Wien and JILA/NIST (USA) succeeded in combining a high-precision optical atomic clock with ...

H5 influenza vaccines: what needs to be done to reduce the risk of a pandemic

2024-09-04

WASHINGTON — As the global threat of H5N1 influenza looms with outbreaks across species and continents including the U.S., three international vaccine and public health experts say it is time to fully resource and support a robust strategy to address this and future potential pandemic influenza threats, including to consider voluntary vaccination for those now at exposure risk. “At this critical juncture, decisions about vaccine development, stockpiling, and deployment will shape our ability to respond to immediate and future pandemic risks,” write Jesse Goodman, MD, PhD; Rick A. Bright, PhD; and Nicole Lurie, MD, ...

Epigenetic changes reprogram astrocytes into brain stem cells

2024-09-04

Resting brain stem cells hardly differ from normal astrocytes, which support the nerve cells in the brain. How can almost identical cells perform such different functions? The key lies in the methylation of their genetic material, which endowes these special astrocytes with stem cell properties. Scientists from the German Cancer Research Center (DKFZ) and Heidelberg University have published their findings in the journal Nature. In mice, the researchers showed that experimentally induced lack of blood ...

Sex hormones modulate the immune system to influence disease risk differently

2024-09-04

Researchers have uncovered how hormones profoundly affect our immune systems, explaining why men and women are affected by diseases differently. Scientists from the Karolinska Institutet in Sweden and Imperial College London have shown for the first time which aspects of our immune systems are regulated by sex hormones, and the impacts this has on disease risk and health outcomes in males and females. It is well established that diseases can affect men and women differently, due to subtle differences ...

Researchers identify mechanism underlying allergic itching, and show it can be blocked

2024-09-04

Why do some people feel itchy after a mosquito bite or exposure to an allergen like dust or pollen, while others do not? A new study has pinpointed the reason for these differences, finding the pathway by which immune and nerve cells interact and lead to itching. The researchers, led by allergy and immunology specialists at Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system, then blocked this pathway in preclinical studies, suggesting a new treatment approach for allergies. The findings are published in Nature. “Our research provides ...

Brain scanning approach shows wiring of depression

2024-09-04

By repeatedly scanning the brains of a small group of patients for a year and a half, Weill Cornell Medicine researchers have identified a distinct pattern of neuronal interactions that appears to predispose some people to developing depression. Published Sept. 4 in Nature, the work highlights the potential of a new “deep scanning” approach to help predict a person’s susceptibility to depression and other neuropsychiatric conditions and may guide the development of novel treatments. Neuroscientists have long relied on functional magnetic resonance imaging (fMRI) to identify patterns of activity ...

Heart drug improved exercise tolerance in clinical trial of patients with hypertrophic obstructive cardiomyopathy

2024-09-04

Exercise intolerance is often severe among patients with cardiovascular disease and can impose significant limitations on their physical abilities and quality of life. Medications known as cardiac myosin inhibitors (CMIs) are being developed to help patients with hypertrophic obstructive cardiomyopathy (HOCM), a disease in which the heart muscle becomes thickened leading to reduced blood flow out of the heart. In a new analysis led by researchers from Mass General Brigham, investigators probed multiple exercise response ...

MD Anderson research highlights for September 4, 2024

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