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
The Silent Battle Within: How Your Organs Choose Between Mom and Dad’s Genes
Research reveals that selective expression of maternal or paternal X chromosomes varies by organ, driven by cellular competition. A new study published today (July 26) in Nature Genetics by the Lymphoid Development Group at the MRC [...]
Study identifies genes increasing risk of severe COVID-19
Whether or not a person becomes seriously ill with COVID-19 depends, among other things, on genetic factors. With this in mind, researchers from the University Hospital Bonn (UKB) and the University of Bonn, in [...]
Small regions of the brain can take micro-naps while the rest of the brain is awake and vice versa
Sleep and wake: They're totally distinct states of being that define the boundaries of our daily lives. For years, scientists have measured the difference between these instinctual brain processes by observing brain waves, with [...]
Redefining Consciousness: Small Regions of the Brain Can Take Micro-Naps While the Rest of the Brain Is Awake
The study broadly reveals how fast brain waves, previously overlooked, establish fundamental patterns of sleep and wakefulness. Scientists have developed a new method to analyze sleep and wake states by detecting ultra-fast neuronal activity [...]
AI Reveals Health Secrets Through Facial Temperature Mapping
Researchers have found that different facial temperatures correlate with chronic illnesses like diabetes and high blood pressure, and these can be detected using AI with thermal cameras. They highlight the potential of this technology [...]
Breakthrough in aging research: Blocking IL-11 extends lifespan and improves health in mice
In a recent study published in the journal Nature, a team of researchers used murine models and various pharmacological and genetic approaches to examine whether pro-inflammatory signaling involving interleukin (IL)-11, which activates signaling molecules such [...]
Promise for a universal influenza vaccine: Scientists validate theory using 1918 flu virus
New research led by Oregon Health & Science University reveals a promising approach to developing a universal influenza vaccine—a so-called "one and done" vaccine that confers lifetime immunity against an evolving virus. The study, [...]
New Projects Aim To Pioneer the Future of Neuroscience
One study will investigate the alterations in brain activity at the cellular level caused by psilocybin, the psychoactive substance found in “magic mushrooms.” How do neurons respond to the effects of magic mushrooms? What [...]
Decoding the Decline: Scientific Insights Into Long COVID’s Retreat
Research indicates a significant reduction in long COVID risk, largely due to vaccination and the virus’s evolution. The study analyzes data from over 441,000 veterans, showing lower rates of long COVID among vaccinated individuals compared [...]
Silicon Transformed: A Breakthrough in Laser Nanofabrication
A new method enables precise nanofabrication inside silicon using spatial light modulation and laser pulses, creating advanced nanostructures for potential use in electronics and photonics. Silicon, the cornerstone of modern electronics, photovoltaics, and photonics, [...]
Caught in the actinium: New research could help design better cancer treatments
The element actinium was first discovered at the turn of the 20th century, but even now, nearly 125 years later, researchers still don't have a good grasp on the metal's chemistry. That's because actinium [...]
Innovative Light-Controlled Drugs Could Revolutionize Neuropathic Pain Treatment
A team of researchers from the Institute for Bioengineering of Catalonia (IBEC) has developed light-activated derivatives of the anti-epileptic drug carbamazepine to treat neuropathic pain. Light can be harnessed to target drugs to specific [...]
Green Gold: Turning E-Waste Into a Treasure Trove of Rare Earth Metals
Scientists are developing a process inspired by nature that efficiently recovers europium from old fluorescent lamps. The approach could lead to the long-awaited recycling of rare earth metals. A small molecule that naturally serves [...]
Cambridge Study: AI Chatbots Have an “Empathy Gap,” and It Could Be Dangerous
A new study suggests a framework for “Child Safe AI” in response to recent incidents showing that many children perceive chatbots as quasi-human and reliable. A study has indicated that AI chatbots often exhibit [...]
Nanoparticle-based delivery system could offer treatment for diabetics with rare insulin allergy
Up to 3% of people with diabetes have an allergic reaction to insulin. A team at Forschungszentrum Jülich has now studied a method that could be used to deliver the active substance into the [...]
Nanorobot kills cancer cells in mice with hidden weapon
Researchers at Karolinska Institutet in Sweden have developed nanorobots that kill cancer cells in mice. The robot's weapon is hidden in a nanostructure and is exposed only in the tumor microenvironment, sparing healthy cells. [...]