Inherent ‘noise’ in the system of gene expression in tumor cell death, is another tool cancer cells use to resist chemotherapy treatment.
Cancer cells have an innate randomness in their ability to respond to chemotherapy, which is another tool in their arsenal of resisting treatment, new research led by the Garvan Institute of Medical Research shows.
Understanding why some tumor cells become resistant to chemotherapy is a core challenge in cancer research, as chemotherapy is still a frontline treatment for most cancers.
“We showed there is ‘noise’ in the process of cell death, which is what happens to cancer cells with chemotherapy treatment – and that this inherent noise, or randomness, in the system of gene expression is an important aspect of chemoresistance,” says Associate Professor David Croucher, Head of the Network Biology Lab at Garvan.
About 15% of people with neuroblastoma don’t respond to chemotherapy treatment.
Neuroblastoma cells (cyan) growing as a tumor and the surrounding collagen matrix (magenta). The cells are expressing a biosensor (JNK-KTR) that reads out single-cell JNK activity in response to chemotherapy treatment. Credit: Max Nobis / Garvan
“Our findings suggest that genetics don’t account for everything; other layers of regulation and other mechanisms of tumor progression can also underpin drug response, so we need to consider them,” says Dr. Sharissa Latham, co-lead author on the study.
The team showed that once neuroblastoma cells reach a state of resisting chemotherapy, they can’t go back, suggesting there is a small window where treatment could work on a tumor cell before it’s locked in.
“Combining chemotherapy with drugs that target this noise within tumors may have the best results as a first-line treatment after diagnosis, before tumors lock into a state of resistance,” says Associate Professor Croucher. This flips on its head the typical protocol for clinical trials in cancer where a new treatment is given to patients who have exhausted all other treatment options.
The new study is published in the journal, Science Advances.
Neuroblastoma cells (cyan) growing as a tumor and the surrounding collagen matrix (magenta). The cells are expressing a biosensor (JNK-KTR) that reads out single-cell JNK activity in response to chemotherapy treatment. Credit: Max Nobis / Garvan
Noise in the tumor system
The researchers used mathematical modeling to narrow down the ‘noise’ signals in the pathways of cell death in neuroblastoma tumors. They then applied that to patient cell samples, using cutting-edge imaging to look at single cells, en masse, to visually isolate the cells that didn’t respond to treatment.
The found a marker for resistance – a set of proteins involved in the process of cell death, known as apoptosis.
“We wanted to figure out what underlies that randomness. What is it about those cells and can anything be manipulated to make them respond,” says Dr. Latham.
The team identified certain classes of approved drugs that might be combined with chemotherapy to stabilize expression of the genes involved in cell death, or by changing the innate threshold that may tip a tumor cell into a resistant state.
The next step is to start progressing the work to clinical trial.
![](https://www.nanoappsmedical.com/wp-content/uploads/2017/05/spacer.jpg)
News
Ethics in Nanomedicine: Key Issues and Principles
Nanomedicine, a branch of nanotechnology, is revolutionizing healthcare by enabling the manipulation of materials at the nanoscale to diagnose, treat, and prevent diseases. Unlike traditional treatments, nanoparticles (NPs) are highly precise in targeting diseased [...]
A call for robust H5N1 influenza preparedness and response
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 [...]
Mucosal COVID-19 boosters outperform mRNA shots in preventing upper airway infections
In a recent study published in Nature Immunology, a team of researchers from the United States used non-human primate models to compare the protection conferred by an intramuscular booster dose of the bivalent messenger ribonucleic acid [...]
How Space Travel Really Changes Astronauts – From the Inside Out
International team reveals previously unknown effects on physiology that could shape the future of long-duration space missions. Researchers have discovered significant changes in the gut microbiome due to spaceflight, which affects host physiology and [...]
Breakthrough in blood stem cell development offers hope for leukemia and bone marrow failure
Melbourne researchers have made a world first breakthrough into creating blood stem cells that closely resemble those in the human body. And the discovery could soon lead to personalized treatments for children with leukemia [...]
Scientists Develop Game-Changing Needle-Free COVID-19 Intranasal Vaccine
A new mucosal COVID-19 vaccine poised to revolutionize the delivery process is especially beneficial for those with a fear of needles. A next-generation COVID-19 mucosal vaccine is set to be a game-changer not only when delivering [...]
Scientists Develop All-in-One Solution To Catch and Destroy “Forever Chemicals”
A new water treatment system developed by UBC researchers efficiently removes and destroys PFAS pollutants using a dual-action catalyst, offering a sustainable and cost-effective solution for water purification challenges. Chemical engineers at the University of [...]
New method accelerates drug discovery from years to months
Researchers from the University of Cincinnati College of Medicine and Cincinnati Children's Hospital have found a new method to increase both speed and success rates in drug discovery. The study, published Aug. 30 in [...]
A new smart mask analyzes your breath to monitor your health
Your breath can give away a lot about you. Each exhalation contains all sorts of compounds, including possible biomarkers for disease or lung conditions, that could give doctors a valuable insight into your health. [...]
Study reveals the role of blood clotting in COVID-19
In a study that reshapes what we know about COVID-19 and its most perplexing symptoms, scientists have discovered that the blood coagulation protein fibrin causes the unusual clotting and inflammation that have become hallmarks [...]
A Novel Cancer Vaccine Combining Nano-11 and ADU-S100
In a recent article published in npj Vaccines, researchers detailed the development of a novel cancer vaccine that combines a plant-derived nanoparticle adjuvant, Nano-11, with a clinically tested STING agonist, ADU-S100. The primary objective was [...]
AI spots cancer and viral infections with nanoscale precision
Researchers have developed an artificial intelligence which can differentiate cancer cells from normal cells, as well as detect the very early stages of viral infection inside cells. The findings, published today in a study [...]
Tiny shards of plastic are increasingly infiltrating our brains, study says
Human brain samples collected at autopsy in early 2024 contained more tiny shards of plastic than samples collected eight years prior, according to a preprint posted online in May. A preprint is a study which has not yet [...]
Scientists Have Discovered Strange DNA in Our Brains – and It Could Be Shortening Our Lives
According to the research, these mitochondrial DNA insertions could be linked to early death. Mitochondria in brain cells frequently insert their DNA into the nucleus, potentially impacting lifespan, as those with more insertions were found to [...]
Watch Out After a Hospital Stay: You Could Be Exposing Your Family to Superbugs
Research indicates hospitals contribute to the local spread of antibiotic-resistant infections. A recent study published in the journal Infection Control & Hospital Epidemiology by the Society for Healthcare Epidemiology of America suggests that family members of [...]
Molecular Trickery: How COVID-19 Silently Sabotages the Human Immune System
Researchers have discovered that SARS-CoV-2 manipulates the human immune system by forcing cells to produce non-functional proteins, hindering the body’s antiviral defenses. This groundbreaking study by teams from prestigious Brazilian universities highlights potential targets for new COVID-19 treatments, [...]