Medical investigators are theorizing that a combination of two treatments that activate myeloid cells may effectively treat a recalcitrant form of pancreatic cancer that thwarts conventional immunotherapy.
Mobilizing the immune system to destroy cancers has been one of the breakthrough treatments of the past decade, spurring the defeat of cancers via immunotherapies that marshal T cells to wage war against malignancies. The problem facing oncologists and their patients is that T cell-based immunotherapy works well for some cancers, but not all forms of the disease.
Activated T cells are extraordinary killers in immunotherapies, and while these lymphoid cells are effective when mobilized against some cancers, there apparently is a role for new strategies, scientists now say.
A research team, affiliated with UNIST has unveiled a novel method to produce a selective anticancer precursor substance that targets and eliminates cancer cells. This groundbreaking method, previously existing only in theory, has now been experimentally proven for the first time, opening up new possibilities in the development of innovative drugs through extensive research on the effects of anticancer precursors on the human body.
Led by Professor Jaeheung Cho of the Department of Chemistry at UNIST, the research team has successfully demonstrated that the synthesis of hydroxymato cobalt (III), a potential candidate substance for anticancer precursors, involves the reaction of metal-active oxygen species with nitrile. Unlike previous studies that relied on expensive heavy metals, this new method utilizes cost-effective metals and operates at lower temperatures.
Using a new technology developed at MIT, diagnosing lung cancer could become as easy as inhaling nanoparticle sensors and then taking a urine test that reveals whether a tumor is present.
The new diagnostic is based on nanosensors that can be delivered by an inhaler or a nebulizer. If the sensors encounter cancer-linked proteins in the lungs, they produce a signal that accumulates in the urine, where it can be detected with a simple paper test strip.
This approach could potentially replace or supplement the current gold standard for diagnosing lung cancer, low-dose computed tomography (CT). It could have an especially significant impact in low- and middle-income countries that don't have widespread availability of CT scanners, the researchers say.
Wellcome Sanger Institute: Cancer Drug Discovery Accelerated as Hundreds of Overlooked Targets Prioritised January 11, 2024
Introduction:
(Eurekalert) A new, systematic analysis of cancer cells identifies 370 candidate priority drug targets across 27 cancer types, including breast, lung and ovarian cancers.
By looking at multiple layers of functional and genomic information, researchers were able to create an unbiased, panoramic view of what enables cancer cells to grow and survive. They identify new opportunities for cancer therapies in a significant leap towards a new generation of smarter, more effective cancer treatments.
In the most comprehensive study of its kind, researchers from the Wellcome Sanger Institute, Open Targets and their collaborators, pooled together data from 930 cancer cell lines. They then used machine learning methods to find the drug targets that show the most promise for developing new treatments, and the patients who would most benefit from such treatments. This involved assessing the occurrence of these targets in actual patient tumours and linking them to specific biological markers and genetic and molecular features found in the tumours.
The findings, published today (11 January) in Cancer Cell, not only bring researchers one step closer to producing a full Cancer Dependency Map of every vulnerability in every type of cancer, but help guide focused efforts to accelerate the development of targeted cancer treatments.
There are many types of cancer that currently lack effective treatments, such as liver and ovarian cancers. Chemotherapy and radiotherapy are effective treatments, but unable to distinguish normal cells from cancerous ones, so can cause damage throughout the entire body with harsh side effects, such as extreme fatigue, nausea and hair loss.
Breast cancer is the most common cancer in women. The development of breast cancer often originates from epithelial cells in the mammary gland—the very cells that specialize in milk production during and after pregnancy.
A team of researchers from Friedrich Schiller University Jena (Germany), the university in Shenzhen (China) and Jena University Hospital (Germany) has taken a closer look at this specialization process and deciphered a molecular mechanism that also appears to play an important role in cancer development.
It may be possible to develop new diagnostic procedures and treatment methods for breast cancer based on these research findings now published in Cell Reports.
Researchers Seek to Improve Blood Tests’ Ability to Detect and Monitor Cancer January 18, 2024
Introduction:
(Eurekalert) CAMBRIDGE, MA -- Tumors constantly shed DNA from dying cells, which briefly circulates in the patient’s bloodstream before it is quickly broken down. Many companies have created blood tests that can pick out this tumor DNA, potentially helping doctors diagnose or monitor cancer or choose a treatment.
The amount of tumor DNA circulating at any given time, however, is extremely small, so it has been challenging to develop tests sensitive enough to pick up that tiny signal. A team of researchers from MIT and the Broad Institute of MIT and Harvard has now come up with a way to significantly boost that signal, by temporarily slowing the clearance of tumor DNA circulating in the bloodstream.
The researchers developed two different types of injectable molecules that they call “priming agents,” which can transiently interfere with the body’s ability to remove circulating tumor DNA from the bloodstream. In a study of mice, they showed that these agents could boost DNA levels enough that the percentage of detectable early-stage lung metastases leapt from less than 10 percent to above 75 percent.
This approach could enable not only earlier diagnosis of cancer, but also more sensitive detection of tumor mutations that could be used to guide treatment. It could also help improve detection of cancer recurrence.
“You can give one of these agents an hour before the blood draw, and it makes things visible that previously wouldn’t have been. The implication is that we should be able to give everybody who’s doing liquid biopsies, for any purpose, more molecules to work with,” says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at MIT, and a member of MIT’s Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science.
AI Harnesses Tumor Genetics to Predict Treatment Response January 18, 2024
Introduction:
(Eurekalert) In a groundbreaking study published on January 18, 2024, in Cancer Discovery, scientists at University of California San Diego School of Medicine leveraged a machine learning algorithm to tackle one of the biggest challenges facing cancer researchers: predicting when cancer will resist chemotherapy.
All cells, including cancer cells, rely on complex molecular machinery to replicate DNA as part of normal cell division. Most chemotherapies work by disrupting this DNA replication machinery in rapidly dividing tumor cells. While scientists recognize that a tumor's genetic composition heavily influences its specific drug response, the vast multitude of mutations found within tumors has made prediction of drug resistance a challenging prospect.
The new algorithm overcomes this barrier by exploring how numerous genetic mutations collectively influence a tumor's reaction to drugs that impede DNA replication. Specifically, they tested their model on cervical cancer tumors, successfully forecasting responses to cisplatin, one of the most common chemotherapy drugs. The model was able to identify tumors at most risk for treatment resistance and was also able to identify much of the underlying molecular machinery driving treatment resistance.
"Clinicians were previously aware of a few individual mutations that are associated with treatment resistance, but these isolated mutations tended to lack significant predictive value. The reason is that a much larger number of mutations can shape a tumor's treatment response than previously appreciated," Trey Ideker, PhD, professor in Department of Medicine at UC San Diego of Medicine, explained. "Artificial intelligence bridges that gap in our understanding, enabling us to analyze a complex array of thousands of mutations at once."
Cancer vaccine with minimal side effects nearing Phase 3 clinical trials.
Source: ABC news, via AOL
Dr. Thomas Wagner, founder of the biotech company Orbis Health Solutions and cancer researcher, has made it his life's mission to find a way to treat cancer without the dreaded side effects that, for some, can become worse than the cancer itself or may even lead to an earlier death.
"The tragedy of cancer is not just that person, the diagnosis, but it's also the fear of the therapy," Wagner told ABC News.
Many traditional cancer treatments, such as chemotherapy, work by killing off cancer cells but also kill off non-cancerous cells throughout the body. This can cause a range of side effects including hair loss, nausea, vomiting, or may knock out a person's immune system putting them at risk of life-threatening infections, Wagner said.
After seeing cancer patients suffer from debilitating side effects of their treatment, Wagner began his mission to develop a cancer treatment that harnessed the power of a person's immune system instead of eliminating it. This treatment was developed as a vaccine that has now been studied for decades, and each shot is completely personalized to each patient.
Scientists Unravel Key Steps in the Road to DNA Repair January 20, 2024
Extract:
(Eurekalert) As we go about our daily lives, our DNA is subjected to all kinds of environmental and internal stress, some of which can lead to breakage of both strands in the double helix. This can be disastrous, and lead to imminent cell death. Luckily, processes like HR (homologous recombination) are continuously repairing this damage.
…
HR enables accurate repair of double-strand breaks, as well as the exchange of genetic information, making it a key part of biodiversity. But the exact biochemical picture of HR, including what happens when (the) RecA (protein) carries both the single and double strands, is not yet clear.
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The team, in cooperation with a team from the Tokyo Metropolitan Institute of Medical Science, adopted two approaches to tackle which of these actually happens. In the first, they used a mutant of RecA which cannot separate the double strands i.e. cannot unwind the strand, to see whether this affected DNA repair. It turns out that this has minimal effect. In the second, they tried to measure how much torsion was created in the strand at different stages of the process. They found that the only torsion (twisting – caltrek) due to unwinding they could detect occurred after the homology search was complete i.e. when strand invasion occurred. For the first time, the team clearly showed that the second model was correct.
Detailed insights into homologous recombination are vital to understanding what happens when things go wrong. For example, factors implicated in breast cancer (BRCA1 and BRCA2) are also responsible for the correct loading of single-stranded DNA onto RAD51, the human version of RecA. This suggests that problems with HR might underlie high incidences of breast cancer in patients with hereditary defects in BRCA1 or BRCA2. The team hopes findings like theirs will lead to new directions for research into cancer.
Rutgers researchers can predict which patients will benefit from a popular prostate cancer drug—and they have devised a strategy that may make the treatment work longer.
"This work should help doctors know which patients' prostate cancers will and won't respond to the androgen deprivation therapy enzalutamide, which can slow prostate cancer growth by disrupting androgen receptor signaling," said Antonina Mitrofanova, associate professor of Biomedical and Health Informatics, associate dean for research at the Rutgers School of Health Professions, researcher at Rutgers Cancer Institute of New Jersey, and lead author of the study.
Researchers have identified a receptor protein known as CHRM1 as a key player in prostate cancer cells' resistance to docetaxel, a commonly-used chemotherapy drug to treat advanced cancer that has spread beyond the prostate.
The discovery opens the door to new treatment strategies that could overcome this resistance. This could ultimately help extend the lives of those with prostate cancer, one of the leading causes of cancer deaths among men.
Led by a team of scientists at Washington State University, the study showed that blocking CHRM1 in resistant prostate cancer cell lines and an animal model based on patient-derived resistant tissue restored docetaxel's ability to kill cells and stop tumor growth. The researchers did this by using dicyclomine, a drug that selectively inhibits CHRM1 activity. Dicyclomine is already on the market as a generic drug and is currently used to treat symptoms of irritable bowel syndrome.
"The effect was pretty dramatic in all the experimental models we tested," said Boyang (Jason) Wu, an associate professor in the WSU College of Pharmacy and Pharmaceutical Sciences and co-senior author on the study. "And because dicyclomine already has a clinical use, this work has immediate translational potential."
Treating complex diseases such as skin cancer often requires simultaneous administration of multiple anticancer drugs. The delivery of such life-saving therapeutic drugs has evolved with the rise of nanotechnology-based drug carriers. Nanoplatforms offer numerous advantages, including increased bioavailability, lowered dosages, and improved biodistribution.
Now a team of researchers, led by Professor Myoung-Hwan Park from Sahmyook University in South Korea, has developed a light-responsive nanofiber-based novel drug delivery system (DDS) targeting skin cancer. The DDS was studied in a detailed manner, beginning with its synthesis and characterization to its biocompatibility, drug release profile, and efficacy against skin cancer. These research findings are published in the Journal of Drug Delivery Science and Technology.
Explaining the motivation behind the present research, Dr. Park states, "Conventional drugs can be efficiently delivered in a controlled manner through nano-engineered platforms, and such an approach increases the overall effectiveness of the treatment. This approach improves outcomes in cancer drug therapy by ensuring precise delivery at optimal dosages."
"Molecular jackhammers" kill cancer by busting through cell walls
By Michael Irving
January 28, 2024
https://phys.org/news/2024-01-sea-metha ... lands.html
Scientists have demonstrated an intriguing new technique to treat cancer – “molecular jackhammers” that latch onto cancer cells, then vibrate vigorously to kill them when activated by infrared light.
Chemotherapy and radiation therapy are currently our most effective treatments for cancer, but they have a shotgun effect, damaging healthy cells all through the body. Worse still, some cancers can develop resistance to these attacks, leaving few other options.
But physical attacks are much harder, if not impossible, for cells to develop resistance to. And that’s the goal with the molecular jackhammers developed by researchers at Texas A&M, Rice University and the University of Texas-MD Anderson Cancer Center.
No matter how important something is, too much of anything is bad for you. Scientists have now put that principle to work to kill cancer, with a new drug that causes calcium to build up and choke the tumor to death.
Calcium ions are crucial messengers in biological cells, and play a key role in keeping the energy-producing mitochondria functioning. They travel in and out of cells through channels that open and close with precise triggers to maintain exactly the right balance. If there’s too much calcium, the cell can suffocate. Now, scientists in South Korea and China have developed a drug that can cause a “calcium storm” inside cells on demand, and shown how to use it to fight cancer.
Chip checks blood to see if cancer treatment is working by fourth week
By Paul McClure
January 29, 2024
Researchers have developed a chip that analyzes a patient’s blood for cells shed by a lung cancer tumor, enabling treating physicians to determine whether lung cancer treatment is working by as early as the fourth week. The information provided by the chip would allow treatment to be adapted to meet patient’s needs and improve outcomes.
The current treatment for stage 3 non-small cell lung cancer (NSCLC), which accounts for about 80% to 85% of lung cancers, is a combination of chemo- and radiation therapy, followed by a year’s worth of immunotherapy. Assessing how a person is responding to treatment and, importantly, whether the cancer is likely to spread requires time, which is not something that every patient has a lot of.
New Technology May Make Cancer Easier for Immune System to Find and Destroy January 29, 2024
Introduction:
(Eurekalert) A new technology to increase visibility of cancer cells to the immune system using CRISPR has been developed, and could lead to a new way to treat cancer.
Major histocompatibility complex (MHC) class I molecules are an immune complex present on the surface of all cells in humans. MHC class I molecules are a prerequisite for the immune system to recognize and eliminate cancer. When cancer cells are faced with pressure from the immune system, they actively reduce their MHC class I molecules, so cancer cells can hide from drawing the attention of CD8+ T cells, the immune system's primary cancer-fighting cells.
Researchers in Japan and the United States, led by Professor Koichi Kobayashi of Hokkaido University and Texas A&M Health Center, and Dr. Paul de Figueiredo, Bond LSC principal investigator and NEXTGEN Precision Health endowed professor at the University of Missouri, have developed technology to robustly augment the amount of MHC class I in cancer cells. This development, a novel method for boosting the immune system's capability to detect and eliminate cancer cells, was published in the journal Proceedings of the National Academy of Sciences.
“Our discovery has the potential to transform the way we approach cancer treatment.” says Kobayashi. “Our technology enables us to specifically target immune responsive genes and activate the immune system against cancer cells, offering hope to those who are resistant to current immunotherapy.”
Destroying Tumor Cells with Calcium January 29, 2024
Introduction:
(Eurekalert) Calcium ions are essential for cells, but can be toxic in higher concentrations. A team of researchers has now designed and prepared a combination drug that kills tumor cells by modulating the calcium influx into the cell. An external calcium source is not necessary because only the calcium ions already present in the tumor tissue are used, according to the study published in the journal Angewandte Chemie.
Biological cells need calcium ions, among other things, for the proper functioning of the mitochondria, the powerhouses of the cells. However, if there is too much calcium, the mitochondrial processes become unbalanced and the cell suffocates. A research group led by Juyoung Yoon of Ewha Womens University in Seoul, South Korea, together with teams from China, has now taken advantage of this process and developed a synergistic antitumor drug that can open calcium channels and thus trigger a deadly calcium storm inside the tumor cell.
The researchers targeted two channels, the first one in the outer membrane, and the other was a calcium channel in the endoplasmic reticulum, a cell organelle that also stores calcium ions. The channel located in the outer membrane opens when it is exposed to a large amount of reactive oxygen species (ROS), while the channel in the endoplasmic reticulum is activated by nitric oxide molecules.
To generate the ROS that open the outer membrane calcium channel, the researchers used the dye indocyanine green. This bioactive agent can be activated by irradiation with near-infrared light, which not only triggers reactions that lead to ROS, but it also heats up the environment. The team explains that the high local temperature activates the other active agent, BNN-6, to release nitric oxide molecules that open the channel in the endoplasmic reticulum.
Following successful trials in tumor cell lines, the team tested an injectable formulation in tumor-implanted mice. To create a biocompatible combined drug, the researchers loaded the active ingredients into tiny modified porous silica beads that are not harmful to the body, but can be recognized by tumor cells and transported into the cell. After injecting the beads into the bloodstream of the mice, the researchers observed that the drug accumulated in the tumor. Exposure to near-infrared light successfully triggered the mechanism of action, and the tumor disappeared after a few days in mice that received the preparation.
Cancer Treatment Two and a Half Times More Effective When Tumours Have Defective "Energy Factories" January 29, 2024
Introduction:
(Eurekalert) Cancer Research UK-funded scientists have made an unusual discovery that could help to identify patients who are up to two and a half times more likely to respond to currently available cancer drugs.
Scientists at the Cancer Research UK Scotland Institute and Memorial Sloan Kettering Cancer Centre in the USA have “rewired” the DNA of mitochondria – energy factories found in every living cell. They found that creating mutations in parts of this DNA determines how well cancer will respond to immunotherapy – treatments which harness the body’s natural defences to attack cancer cells.
This discovery opens up new ways to identify patients who could benefit most from immunotherapy by testing for mitochondrial DNA mutations. Half of all cancers have mitochondrial DNA (mtDNA) mutations and this discovery shows for the first time that they could be exploited to improve cancer treatment.
In the future, combining treatments that mimic the effect of these mutations with immunotherapy could increase the chances of successful treatment for multiple types of cancer.
In a paper published in the journal Nature Cancer today (Monday 29th January), the scientists demonstrate for the first time a direct link between mitochondrial DNA (mtDNA) mutations and response to cancer treatment. Surprisingly, they found that tumours with high levels of mtDNA mutations are up to two and a half times more likely to respond to treatment with an immunotherapy drug called nivolumab.
Researchers have created model tumors using the tissues of patients with advanced bowel cancer and used them to predict how the disease will respond to specific drug therapies – before treatment begins. Found to be 83% accurate, the pioneering approach would increase the chances that patients receive the most effective treatment at the earliest opportunity.
Bowel cancer is the second leading cause of cancer-related death worldwide despite an increasing number of treatment options. If caught early enough, the cancer can be treated successfully, but one of the biggest challenges is determining how a patient will respond to that treatment. A trial-and-error approach is taken for most therapies as no markers are available to predict response. As a result, patients can receive ineffective, costly, and toxic drugs.
In a pioneering study, researchers at the Walter and Eliza Hall Institute (WEHI) in Melbourne, Australia, developed a novel method of accurately predicting how a patient with advanced bowel cancer will respond to treatment – before they receive it.
“Each time you give a patient an ineffective treatment, you lose two to three months on something that won’t work,” said Peter Gibbs, a study co-author. “The window for successful treatment is often limited, so it is vital that we choose the options with the highest chance of success and avoid other treatments that are unlikely to work.”
The researchers created patient-derived tumor organoids (PDTOs), grain-of-sand-sized organs grown from a patient’s tumor tissues that mirror the features of the original tumor, from 30 patients in the advanced stages of bowel cancer. The PDTOs were then tested for their sensitivity to a range of cancer-fighting drugs.
