Health
Rethinking How Cancer Cells Evade Targeted Therapy
Glioblastomas (GBMs) are incurable brain tumors with a prognosis of about one-and-a half years on average. They are highly resistant to treatment and have defied all attempts at precision therapy.
UCSF Researchers Identify the Cellular Source of Recurrent Glioma
Newswise — Glioblastomas (GBMs) are incurable brain tumors with a prognosis of about one-and-a half years on average. They are highly resistant to treatment and have defied all attempts at precision therapy.
In their study publishing December 20 in Nature Cancer, first author Lin Wang, PhD and senior author Aaron Diaz, PhD, found that phenotype switching, as opposed to genetic evolution, may be the escape mechanism that explains the failure of precision therapies to date. They found that some cells shift to a mesenchymal, radiation-resistant phenotype (state) as a stress response following standard therapy.
Credit: UCSF
Aaron Diaz, PhD, Associate Professor, Neurological Surgery, UCSF Weill Institute for Neurosciences
“We asked if there is another mechanism that explains therapeutic resistance,” said Diaz, associate professor of neurological surgery at the UCSF Weill Institute for Neurosciences. “Our study concludes that, rather than a genetic evolution, there is a phenotypic plasticity or transition which allows these cells to evade therapy.”
To identify what drives treatment resistance to standard therapy, as well as the cellular source of recurrent disease, UCSF researchers used single-nucleus RNA, open-chromatin, spatial profiling to analyze 86 primary-recurrent, patient-matched, paired GBM specimensThis unprecedented cohort represented decades of biobanking at UCSF.
With access to thirty years’ worth of GBM’s, the scientists were able to present novel cell-intrinsic and cell-extrinsic targets as well as a single-cell multi-omics atlas of GBM under therapy. This was the first time that researchers were able to comprehensively map intra-cellular signaling in the tumor-anatomical niches of recurrent GBM and identify novel cell-extrinsic therapeutic targets.
The 86 specimens contained the cellular tumor and adjacent non-malignant tissue from the surgical margin. This unique cohort enabled Diaz and his team to analyze communications between malignant and non-malignant glia. They found that cells in this surgical margin acted as niches of recurrence where non-malignant glia were broadcasting pro-growth signals that influenced the tumor cells to regrow. These paracrine (cell extrinsic) signals stimulated the activator protein (AP1) pathway, leading to mesenchymal transition, therapy resistance and tumor recurrence.
These mesenchymal transitions were apparent in the tumor samples after therapy, along with increased numbers of cycling mesenchymal cells. Pro-growth signals from the tumor microenvironment, as well as the cell-intrinsic response to radiation therapy, drove the mesenchymal shift through a stress-response pathway mediated by AP1.
The researchers were able to combine two techniques to achieve a map of paracrine signals – single-nucleus RNA-sequencing of frozen tissue specimens and spatial transcriptomics profiling of formalin-fixed specimens. From each tumor biopsy, they performed single-nucleus RNA-seq which measures transcriptome-wide gene expression in individual cells, for thousands of cells at a time. They compared the expression of signal receptors to that of their known ligands, between the different cell populations sequenced. They then validated that cells from these populations physically interact and signal in situ, using spatial transcriptomics.
“This is the first single-cell longitudinal study of this scale in glioma,” said Diaz. “It’s also a study that could be done only at UCSF, because it represents decades of careful biobanking of surgical specimens. Since all the specimens came from UCSF, we know that the treatment histories are homogeneous, in that each patient received only standard-of-care therapy. It’s both this cohort’s scale and treatment uniformity that enable us to see past patient specific effects to the underlying biology of the disease.”
The research was supported in part by the UCSF GBM Precision Medicine Program.
Authors: Other UCSF authors include: Jangham Jung, Husam Babikir, Karin Shamardani, Saket Jain, Xi Feng, Nalin Gupta, Susanna Rosi, Susan Chang, David Raleigh of the UCSF Department of Neurological Surgery; David Solomon of the UCSF Department of Pathology, and Joanna J. Phillips of the UCSF Departments of Neurological Surgery and Pathology.
Funding: This work has been supported by research awards from: NIH/NLM R01LM013897 and UC/CRCC CRN-19-586041 to A.D.; the UCSF Glioma Precision Medicine Program to A.D., S.C., J.J.P., D.S.; NIH/NINDS R01CA246722 to A.D, N.G., and S.R.; UCSF Brain Tumor SPORE Biorepository NIH/NCI 5P50CA097257 to J.J.P.; a gift from the Panattoni family to A.D. and J.J.P.
About UCSF Health: UCSF Health is recognized worldwide for its innovative patient care, reflecting the latest medical knowledge, advanced technologies and pioneering research. It includes the flagship UCSF Medical Center, which is ranked among the top 10 hospitals nationwide, as well as UCSF Benioff Children’s Hospitals, with campuses in San Francisco and Oakland, Langley Porter Psychiatric Hospital and Clinics, UCSF Benioff Children’s Physicians and the UCSF Faculty Practice. These hospitals serve as the academic medical center of the University of California, San Francisco, which is world-renowned for its graduate-level health sciences education and biomedical research. UCSF Health has affiliations with hospitals and health organizations throughout the Bay Area. Visit https://ucsfhealth.org. Follow UCSF Health on Facebook or on Twitter.
Source: University of California, San Francisco (UCSF)
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(Family Features) Staying up to date on recommended vaccines is important during pregnancy. This is especially true during the winter months when more people tend to get sick from flu, COVID-19 and RSV. These viruses can be especially dangerous for pregnant people and babies.
Vaccines are an important part of routine pregnancy care, both for you and your baby. Getting vaccinated against flu and COVID-19 can cut your risk of hospitalization by about half.
Now is the time to get vaccinated if you haven’t already. Flu vaccines help protect you from getting the flu and getting seriously ill, so it’s a good idea to schedule an appointment now. The latest COVID-19 vaccines are important too because they lower your risk of serious illness. An RSV vaccine may also be recommended for when you are 32-36 weeks pregnant. Be sure to talk to your doctor.
“Right now, we are seeing a concerning increase in cases of respiratory diseases, such as the flu, COVID-19 and RSV,” said Adm. Rachel Levin, MD, assistant secretary for health at the U.S. Department of Health and Human Services. “I encourage all pregnant people to take preventive action to protect their health and the health of their baby. The best and safest way to do this is to get vaccinated. Getting vaccinated is easy and is usually covered by insurance.”
Help Protect Your Baby
When you get flu, COVID-19 and RSV vaccines, you’re helping protect your baby by passing your immunity on to them. Getting vaccinated against flu, COVID-19 and RSV during pregnancy can protect your baby during the first 6 months of life. These viruses can be very harmful to newborns. In fact, RSV is the leading cause of hospitalization in infants
Talk to Your Doctor About Timing
Millions of people in the U.S. have already gotten vaccinated against flu, COVID-19 and RSV this season. If you haven’t gotten your vaccines yet, be sure to talk with your doctor. They can help you choose the right vaccines and determine the best timing to help protect you and your baby.
Get the Facts
Getting vaccinated can give you peace of mind, ensuring you have done everything you can to protect yourself and your baby from serious respiratory illness. Information can give you power and comfort, especially when you’re pregnant.
Go to cdc.gov/RiskLessDoMore to learn more about flu, COVID-19 and RSV vaccines, or go to vaccines.gov to get started today.
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U.S. Department of Health and Human Services
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Lifestyle
Here’s to a Healthy New Year: What your family needs to know about vaccines
Vaccines for flu, COVID-19, and RSV are vital for family health, especially as respiratory viruses increase during colder months. Stay updated to reduce serious illness and hospitalizations.
(Family Features) This year, make a plan to keep your family healthy by helping them get vaccinated for respiratory infections like flu, COVID-19 and RSV. These respiratory illnesses are more likely to become serious for people who are not up to date on their vaccines.
In colder months, respiratory viruses tend to surge, and people spend more time indoors where they are more likely to be exposed. These respiratory infections can cause serious illness and hospitalization. This season’s flu and COVID-19 vaccines, as well as the RSV vaccine, are the best way to help your family risk less serious illness and do more of what they enjoy.
What should your family know?
Vaccines can keep you and your family from getting very sick from respiratory illnesses. The Centers for Disease Control and Prevention (CDC) recommends everyone ages 6 months and older get this season’s flu and COVID-19 vaccines.
In addition, all adults ages 75 and older – and those ages 60 and older with certain health conditions or who live in a nursing home – should get one dose of an RSV vaccine if they haven’t before. Pregnant people should also talk to their doctor about getting an RSV vaccine to protect their baby during their first 6 months of life.
Is your family at high risk?
It’s important to know the risks of getting very sick from flu, COVID-19 or RSV. According to the CDC, some people have a higher risk than others, including:
- People not up to date on their vaccines: Vaccines cut your risk of needing hospital care for flu or COVID-19 by about half, according to the CDC. In 2023, 90% of adults admitted to the hospital for COVID-19 were not up to date on their COVID-19 vaccine. People who skipped their flu shot were twice as likely to need to see a doctor for the flu.
- Older adults: Most flu, COVID-19 and RSV deaths are in people ages 65 and older. If you help care for an older family member or friend, let them know vaccines are their best protection from getting very sick.
- People with underlying health conditions: Heart and lung disease, diabetes, kidney disease and other chronic conditions can cause complications and more severe illness from flu, COVID-19 and RSV.
- Those who live in long-term care: Respiratory viruses can be a greater threat to older people in long-term care, who often have health issues that raise their risk of severe flu, COVID-19 or RSV.
- Pregnant people: Pregnancy raises the risk of severe illness from flu and COVID-19. Getting vaccinated during pregnancy helps protects the pregnant person and baby. An RSV vaccine during pregnancy protects the baby from severe RSV in their first 6 months of life.
Get your family vaccinated now for a healthy new year
Join the millions of people who’ve already gotten vaccinated this season. Take your family to get vaccinated now to risk less severe illness and do more of what you enjoy. It’s safe to get flu and COVID-19 vaccines (and an RSV vaccine, if eligible) at the same time.
Visit cdc.gov/RiskLessDoMore to learn more about flu, COVID-19 and RSV vaccines. Talk with your doctor about which vaccines are right for you or go to vaccines.gov to find a nearby pharmacy. You can order free COVID-19 test kits (up to four per household) at COVIDTests.gov.
Know Your Risk
In the United States, there are additional groups of people who are at higher risk from these respiratory illnesses.
- People in rural parts of the country: Vaccines matter even more in rural areas where there may be fewer doctors or clinics to help people who get very sick. Yet in these regions, less than half of adults got a flu vaccine last year. Fewer than 1 in 5 got an updated COVID-19 vaccine.
- Black and Hispanic people: At last year’s respiratory virus peak, Black people were more likely than white and Hispanic people to be in the hospital for flu, COVID-19 or RSV. By the end of last year’s virus season, Hispanic people were more likely than non-Hispanic white people to have been in the hospital for flu.
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SOURCE:
U.S. Department of Health and Human Services
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health and wellness
What Pregnant People Need to Know About Vaccines for a Healthy New Year
The New Year brings hope for pregnant individuals, emphasizing health and preventing respiratory illnesses like flu, COVID-19, and RSV through vaccination, which benefits both mother and infant.
(Family Features) A new year can bring feelings of hope and optimism. This can be especially true for pregnant people as they look forward to the arrival of their baby. Keeping themselves and their baby healthy is also a great New Year’s goal, and in the colder months, that means avoiding respiratory illnesses. Flu, COVID-19 and RSV – which are common in many parts of the country right now – can become severe, sometimes requiring hospital care.
Vaccines are the best protection against severe respiratory illness. They cut your risk of being in the hospital for flu or COVID-19 by about half and for RSV by about 70%, according to the Centers for Disease Control and Prevention. Vaccines help pregnant people risk less severe illness and focus on preparing for their new baby.
How do vaccines protect pregnant people and babies?
Flu, COVID-19 and RSV can be very harmful to infants, especially in their first 6 months of life. Infants are at higher risk for serious flu-related illness and are hospitalized for COVID-19 at about the same rate as adults ages 65-74. RSV is the leading cause of infant hospitalization.
Getting vaccinated for flu and COVID-19 during your pregnancy can provide protection from serious respiratory illness for both you and for your infant in their first 6 months. Your immunity is passed along to your baby before birth.
An RSV vaccine during pregnancy can also protect your baby from severe RSV in their first 6 months. An RSV vaccine is recommended during weeks 32 through 36 of pregnancy if that period falls from September through January when RSV is more common.
It is safe for a pregnant person to get these vaccines at the same time. Any side effects from the vaccines are usually mild and go away on their own in a few days.
Get vaccinated for a healthy new year
Talk to your doctor or visit cdc.gov/RiskLessDoMore to learn more about flu, COVID-19 and RSV vaccines. Find a pharmacy near you at vaccines.gov. You can also order free COVID-19 test kits (up to four per household) at COVIDTests.gov.
Photo courtesy of Shutterstock
SOURCE:
U.S. Department of Health and Human Services
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