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.
News
Cutting Two Amino Acids Slowed Prostate Cancer in Mice
A newly identified link between amino acid metabolism and cholesterol production may help prostate tumors adapt to hormone therapy. Prostate cancer can find ways around treatments designed to deprive tumors of the hormones they [...]
Largest-Ever Physics Survey Raises New Doubts About Our Model of the Universe
Physicists around the world remain deeply divided on key mysteries of the universe, from dark matter to quantum gravity. The standard cosmological model failed to gain majority support, and no leading theory dominated the [...]
Scientists Just Overturned a 100-Year-Old Belief About Bacteria in the Lungs
New findings raise questions about the role of microbes living in the lungs. More than 35 trillion bacteria live throughout the human body, forming microbiomes in the gut, mouth, lungs, skin, and urogenital tract. [...]
GHCE Concept
From the preface of the book Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artificial Intelligence, Edited by Frank Boehm: Since the publication of my first book (Nanomedical Device and Systems [...]
Novartis, Ionis drug failure spurs questions
Pelacarsen didn’t protect heart health despite lowering levels of a protein particle, “Lp(a),” in a large clinical trial — a result with important implications for cardiovascular drug research. Dive Brief: An RNA drug from [...]
New injectable treatment helps the brain rebuild after stroke
Biomedical engineers at Duke University have created an injectable biomaterial that may help the brain recover from damage left behind by an ischemic stroke. In experiments with mice, the material transformed the cavity created [...]
Scientists Discover a Hidden “Immune Organ” Inside the Skull
Researchers discovered lymph node-like immune hubs inside skull bone marrow that appear to act as rapid-response centers for the brain. For decades, the brain was thought to operate largely apart from the immune system. [...]
Engineered tRNAs and lipid nanoparticles target nonsense mutation cystic fibrosis
Researchers have developed a potential new approach for treating a form of cystic fibrosis caused by so-called nonsense mutations, combining chemically modified transfer RNAs with lipid nanoparticles designed to deliver the therapy directly to [...]
New pancreatic cancer drug carries a $39,800 monthly list price
A groundbreaking treatment for one of the most common forms of pancreatic cancer has been approved in pill form by the FDA. Revolution Medicines’ oral tablet daraxonrasib, branded as Rasonque, reduced the risk of [...]
Researchers Have Discovered a New Way To Reduce Chronic Nerve Pain
A cancer-linked protein called BRAF may help drive chronic nerve pain, and existing cancer drugs targeting it reduced pain sensitivity in preclinical models. Chronic nerve pain can persist long after an injury and often [...]
Our books now available worldwide!
Online Sellers other than Amazon, Routledge, and IOPP Indigo Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artifcial Intelligence Global Health Care Equivalency In The Age Of Nanotechnology, Nanomedicine And Artificial [...]
Quantum-Enabled Regenerative Health: Reimagining Wellness, Precision Health and Longevity Medicine
Introduction Healthcare is approaching a frontier where the quantum portfolio could influence not only how disease is diagnosed and treated, but how health itself is measured, modeled, predicted and preserved. Quantum computing, quantum simulation, [...]
FDA Clears First-of-Its-Kind Nonmedication Treatment for PTSD
The FDA has cleared a system that uses brain activity data to personalize magnetic stimulation for PTSD, adding a new nonmedication treatment option. Every day in the United States, approximately 17.5 veterans die by suicide, [...]
FDA approves breakthrough drug to treat advanced pancreatic cancer
The Food and Drug Administration (FDA) approved on Wednesday a drug that could extend the survival of those with metastatic pancreatic cancer. The drug, called daraxonrasib, will be sold under the brand name Rasonque [...]
AI Decodes a Hidden DNA Signal Linked to Disease-Causing Mutations
Machine learning identifies the likely “initiator” and enables new predictions about DNA mutations that can cause disease. Every human cell depends on tens of thousands of genes being switched on at the right time [...]
Pope Leo Urges Global Response to Congo’s Deadliest Ebola Outbreak
Pope Leo called for international action to address the Ebola outbreak in the Democratic Republic of Congo. The epidemic has claimed over 2,500 lives and is the nation's largest recorded outbreak. The Pope emphasized [...]
