PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Scientists glue two proteins together, driving cancer cells to self-destruct

Stanford Medicine researchers hope new technique will flip lymphoma protein’s normal action — from preventing cell death to triggering it

2024-11-27
(Press-News.org) Our bodies divest themselves of 60 billion cells every day through a natural process of cell culling and turnover called apoptosis.

These cells — mainly blood and gut cells — are all replaced with new ones, but the way our bodies rid themselves of material could have profound implications for cancer therapies in a new approach developed by Stanford Medicine researchers.

They aim to use this natural method of cell death to trick cancer cells into disposing of themselves. Their method accomplishes this by artificially bringing together two proteins in such a way that the new compound switches on a set of cell death genes, ultimately driving tumor cells to turn on themselves. The researchers describe their latest such compound in a paper published Oct. 4 in Science.

The idea came to Gerald Crabtree, MD, a professor of development biology, during a pandemic stroll through the forests of Kings Mountain, west of Palo Alto, California. As he walked, Crabtree, a longtime cancer biologist, was thinking about major milestones in biology.

One of the milestones he pondered was the 1970s-era discovery that cells trigger their own deaths for the greater good of the organism. Apoptosis turns out to be critical for many biological processes, including proper development of all organs and the fine-tuning of our immune systems. That system retains pathogen-recognizing cells but kills off self-recognizing ones, thus preventing autoimmune disease.

“It occurred to me, Well gee, this is the way we want to treat cancer,” said Crabtree, a co-senior author on the study who is the David Korn, MD, Professor in Pathology. “We essentially want to have the same kind of specificity that can eliminate 60 billion cells with no bystanders, so no cell is killed that is not the proper object of the killing mechanism.”

Traditional treatments for cancer — namely chemotherapy and radiation — often kill large numbers of healthy cells alongside the cancerous ones. To harness cells’ natural and highly specific self-destruction abilities, the team developed a kind of molecular glue that sticks together two proteins that normally would have nothing to do with one another.

Flipping the cancer script

One of these proteins, BCL6, when mutated, drives the blood cancer known as diffuse large cell B-cell lymphoma. This kind of cancer-driving protein is also referred to as an oncogene. In lymphoma, the mutated BCL6 sits on DNA near apoptosis-promoting genes and keeps them switched off, helping the cancer cells retain their signature immortality.

The researchers developed a molecule that tethers BCL6 to a protein known as CDK9, which acts as an enzyme that catalyzes gene activation, in this case, switching on the set of apoptosis genes that BCL6 normally keeps off.

“The idea is, Can you turn a cancer dependency into a cancer-killing signal?” asked Nathanael Gray, PhD, co-senior author with Crabtree, the Krishnan-Shah Family Professor and a chemical and systems biology professor. “You take something that the cancer is addicted to for its survival and you flip the script and make that be the very thing that kills it.”

This approach — switching something on that is off in cancer cells — stands in contrast to many other kinds of targeted cancer therapies that inhibit specific drivers of cancer, switching off something that is normally on.

“Since oncogenes were discovered, people have been trying to shut them down in cancer,” said Roman Sarott, PhD, a postdoctoral scholar at Stanford Medicine and co-first author on the study. “Instead, we’re trying to use them to turn signaling on that, we hope, will prove beneficial for treatment.”

When the team tested the molecule in diffuse large cell B-cell lymphoma cells in the lab, they found that it indeed killed the cancer cells with high potency. They also tested the molecule in healthy mice and found no obvious toxic side effects, even though the molecule killed off a specific category of of the animals’ healthy B cells, a kind of immune cell, which also depend on BCL6. They’re now testing the compound in mice with diffuse large B-cell lymphoma to gauge its ability to kill cancer in a living animal.

Because the technique relies on the cells’ natural supply of BCL6 and CDK9 proteins, it seems to be very specific for the lymphoma cells — the BCL6 protein is found only in this kind of lymphoma cell and in one specific kind of B cell. The researchers tested the molecule in 859 different kinds of cancer cells in the lab; the chimeric compound killed only diffuse large cell B-cell lymphoma cells.

And because BCL6 normally acts on 13 different apoptosis-promoting genes, the researchers hope their strategy will avoid the treatment resistance that seems so common in cancer. Cancer is often able to rapidly adapt to therapies that target only one of the disease’s weak spots, and some of these therapies may stop cancer from growing without killing the cells entirely. The research team hopes that by blasting the cells with multiple different cell death signals at once, the cancer will not be able to survive long enough to evolve resistance, although this idea remains to be tested.

“It’s sort of cell death by committee,” said Sai Gourisankar, PhD, a postdoctoral scholar and co-first author on the study. “And once a cancer cell is dead, that’s a terminal state.”

Crabtree and Gray, both members of the Stanford Cancer Institute, are co-founders of a biotech startup, Shenandoah Therapeutics, that aims to further test this molecule and a similar, previously developed molecule in hopes of gathering enough pre-clinical data to support launching clinical trials of the compounds. They also plan to build similar molecules that could target other cancer-driving proteins, including the oncogene Ras, which is a driver of several different kinds of cancer.

The study was funded by the Howard Hughes Medical Institute, the National Institutes of Health (grants CA276167, CA163915, MH126720-01 and 5F31HD103339-03), the Mary Kay Foundation, the Schweitzer Family Fund, the SPARK Translational Research Program at Stanford University and Bio-X at Stanford University.

# # #

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu.

END



ELSE PRESS RELEASES FROM THIS DATE:

Intervention improves the healthcare response to domestic violence in low- and middle-income countries

Intervention improves the healthcare response to domestic violence in low- and middle-income countries
2024-11-27
Culturally appropriate women-centred interventions can help healthcare systems respond to domestic violence, research has found. HERA (Healthcare Responding to Violence and Abuse) has been co-developing and evaluating a domestic violence and abuse healthcare intervention in low- and middle-income countries for the past five years. This National Institute for Health and Care Research (NIHR) Global Research Group will report their findings, and publish a PolicyBristol report, at a conference in London today ...

State-wide center for quantum science: Karlsruhe Institute of Technology joins IQST as a new partner

State-wide center for quantum science: Karlsruhe Institute of Technology joins IQST as a new partner
2024-11-27
The mission of IQST is to further our understanding of nature and develop innovative technologies based on quantum science by leveraging synergies between the natural sciences, engineering, and life sciences. "Many KIT scientists already successfully support IQST with their expertise as Fellows. All the more I am pleased that the Karlsruhe Institute of Technology is now joining our interdisciplinary centre as an institution," says IQST Director Prof. Stefanie Barz. "This will strengthen networking within the academic quantum community in Baden-Württemberg," emphasizes ...

Cellular traffic congestion in chronic diseases suggests new therapeutic targets

Cellular traffic congestion in chronic diseases suggests new therapeutic targets
2024-11-27
***Embargoed until November 27 at 11 AM EST*** Chronic diseases like type 2 diabetes and inflammatory disorders have a huge impact on humanity. They are a leading cause of disease burden and deaths around the globe, are physically and economically taxing, and the number of people with such diseases is growing. Treating chronic disease has proven difficult because there is not one simple cause, like a single gene mutation, that a treatment could target. At least, that’s how it has appeared to scientists. However, research from Whitehead Institute Member Richard Young and colleagues, published in the journal ...

Cervical cancer mortality among US women younger than age 25

2024-11-27
About The Study: This study found a steep decline in cervical cancer mortality among U.S. women younger than 25 years between 2016 and 2021. This cohort of women is the first to be widely protected against cervical cancer by human papillomavirus (HPV) vaccines. The findings from this study in the context of other published research suggest that HPV vaccination affected the sequential decline in HPV infection prevalence, cervical cancer incidence, and cervical cancer mortality.  Corresponding ...

Fossil dung reveals clues to dinosaur success story

Fossil dung reveals clues to dinosaur success story
2024-11-27
In an international collaboration, researchers at Uppsala University have been able to identify undigested food remains, plants and prey in the fossilised faeces of dinosaurs. These analyses of hundreds of samples provide clues about the role dinosaurs played in the ecosystem around 200 million years ago. The findings have been published in the journal Nature. “Piecing together ‘who ate whom’ in the past is true detective work,” says Martin Qvarnström, researcher at the Department of Organismal Biology and lead author of the study. “Being able to examine what animals ate and how they interacted with their environment helps us understand what enabled ...

New research points way to more reliable brain studies

2024-11-27
Brain-wide association studies, which use magnetic resonance imaging to identify relationships between brain structure or function and human behavior or health, have faced criticism for producing results that often cannot be replicated by other researchers.  A new study published in Nature demonstrates that careful attention to study design can substantially improve the reliability of this type of research. For the study, Kaidi Kang, a biostatistics PhD student, Simon Vandekar, PhD, associate professor of Biostatistics, and colleagues analyzed data from more than 77,000 brain scans across 63 studies.  The ...

‘Alzheimer’s in dish’ model shows promise for accelerating drug discovery

2024-11-27
A decade ago, researchers introduced a new model for studying Alzheimer’s disease. Known as “Alzheimer’s in a dish,” the model uses cultures of mature brain cells suspended in a gel to recapitulate what takes place in the human brain over 10 to 13 years in just six weeks. But does the model truly produce the same changes that take place in patients? In a new study, researchers from Mass General Brigham, in collaboration with colleagues at Beth Israel Deaconess Medical Center (BIDMC), created an algorithm to assess, in an unbiased manner, how well models of Alzheimer’s disease ...

Ultraprocessed food intake and psoriasis

2024-11-27
About The Study: The results of this study showed an association between high ultraprocessed food intake and active psoriasis status. After adjustments for age, body mass index (BMI), alcohol intake, and comorbidities, the results remained significant, suggesting that ultraprocessed food intake has a proinflammatory action separate from high BMI. Corresponding Author: To contact the corresponding author, Emilie Sbidian, MD, PhD, email emilie.sbidian@aphp.fr. To access the embargoed study: ...

Race and ethnicity, gender, and promotion of physicians in academic medicine

2024-11-27
About The Study: The findings of this study indicate that preferential promotion of white men within academic medicine continues to persist in the new millennium, with racially and ethnically diverse women experiencing greater underpromotion. To achieve a workforce that reflects the diversity of the U.S. population, this study suggests that academic medicine needs to transform its culture and practices surrounding faculty appointments and promotions. Corresponding Author: To contact the corresponding author, Lauren Clark, MS, email lclark5@kumc.edu. To access the embargoed study: ...

Testing and masking policies and hospital-onset respiratory viral infections

2024-11-27
About The Study: In this study, stopping universal masking and SARS-CoV-2 testing was associated with a significant increase in hospital-onset respiratory viral infections relative to community infections. Restarting the masking of health care workers was associated with a significant decrease.  Corresponding Author: To contact the corresponding author, Theodore R. Pak, MD, PhD, email tpak@mgh.harvard.edu. To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ (doi:10.1001/jamanetworkopen.2024.48063) Editor’s ...

LAST 30 PRESS RELEASES:

Empowering older adults with home-care robots

New concept for sustainable fuel cell polymer electrolytes overcomes barriers in high-temperature, low-humidity use, advancing net-zero carbon goals

Sculpting the brain (without chisel or scalpel)

Wrong trees in the wrong place can make cities hotter at night, study reveals

New gene therapy reverses heart failure in large animal model

Young children less likely than adults to see discrimination as harmful

Tiny poops in the ocean may help solve the carbon problem

Study offers insight into chloroplast evolution

Advancing the synthesis of two-dimensional gold monolayers

Human disruption is driving ‘winner’ and ‘loser’ tree species shifts across Brazilian forests

A novel heme-model compound that treats lethal gas poisoning

Shape-changing device helps visually impaired people perform location task as well as sighted people - EMBARGO: Tuesday 10 December (10:00 UK time)

AI predicts that most of the world will see temperatures rise to 3°C much faster than previously expected

Second round of FRONTIERS Science Journalism Residency Program awards grants to ten journalists

The inequity of wildfire rescue resources in California

Aerosol pollutants from cooking may last longer in the atmosphere – new study

Breakthrough in the precision engineering of four-stranded β-sheets

Family income predicts adult problems more than neighborhood poverty

Leading stress expert Ron de Kloet on hormone's dual nature: From protection to harm

Almost half of young vapers are able to stop with quitline help

After a divisive election, most U.S. adults ready to avoid politics this holiday

Food insecurity in LA County remains well above national average, despite slight decline

People with a positive attitude are built differently

AML, sickle cell disease research among highlights of UC ASH abstracts

Dozens of presentations advance multiple myeloma research at the 2024 American Society for Hematology (ASH) meeting

ASH 2024: Study shows that genetic mutations accumulate in smokers with myelodysplastic syndromes and worsen outcomes

Nature inspires self-assembling helical polymer

Could US-style summer holiday programs boost Aussie kids’ health?

Towards safer, higher performance batteries through network topology optimization

ASH: Triplet combination regimens demonstrate high response rates in multiple leukemias

[Press-News.org] Scientists glue two proteins together, driving cancer cells to self-destruct
Stanford Medicine researchers hope new technique will flip lymphoma protein’s normal action — from preventing cell death to triggering it