Researchers at the Spanish National Cancer Research Centre (CNIO), led by Dr. Manuel Valiente, have uncovered how cancer cells that have spread to the brain (metastasis) are able to resist the effects of radiotherapy. The study reveals a new biomarker that could be detected in a simple blood test to indicate whether a patient will respond to radiotherapy. The researchers also discovered a specific type of drug, called a RAGE inhibitor, which can enter the brain and reverse the resistance to radiotherapy. Clinical studies are now being started by the team to validate their findings in people.
When cancer progresses, it often spreads to the brain, where it becomes much more difficult to treat. In patients with solid tumors such as lung cancer, breast cancer or melanoma, it eventually spreads to the central nervous system in 20-40% of cases. Unfortunately, most patients pass away within 12 months of finding out this has happened.
A research team based at the University of Ottawa and The Ottawa Hospital has developed a virus that infects and kills cancer cells without harming normal cells, while also sending out signals to prepare nearby uninfected cancer cells for viral attack. Their new study, published in Nature Communications, shows that this novel strategy can shrink tumors and significantly prolong survival in several cancer models in mice.
The strategy relies on extracellular vesicles, tiny particles that pinch off from a cell and fuse with other cells. The research team created a virus that causes infected cells to produce extracellular vesicles filled with a specific RNA that blunts the antiviral defenses of nearby cancer cells. They found that this novel virus can work with other forms of immunotherapy, as well as with small-molecule drugs, to enhance cancer-killing even further.
"Cancer cells are constantly evolving new ways to evade our therapies, so we designed this therapy to target cancer on multiple fronts at the same time," said senior author Dr. Carolina Ilkow, Assistant Professor in the Faculty of Medicine and Senior Scientist at The Ottawa Hospital. "We believe these observations are transformative for the fields of oncolytic viruses, miRNA therapeutics and exosome-based therapies."
The researchers note that while many groups are investigating therapies based on RNA and extracellular vesicles, these therapies are much more difficult to manufacture and store than viral therapies. This new viral technology could have a broad impact, as it provides an easy and targeted way to "manufacture" and deliver RNA therapeutics and extracellular vesicles right inside the patient, rather than in a lab.
During the first nine months of the COVID-19 pandemic, pediatric cancer patients from lower- and middle-income countries faced a higher risk of all-cause mortality than those in high-income countries, according to data presented at the AACR Annual Meeting 2022, held April 8-13.
This study was concurrently published in BMJ Open.
Pediatric cancer, while rare, is the world's second leading noncommunicable cause of death among children. Research has shown that survival rates from childhood cancers are dramatically different in lower- and middle-income countries (LMICs) compared with high-income countries (HICs), explained the study's presenter, Muhammed Elhadi, MBBCh, a medical doct
A new type of immunotherapy making use of the immune system's "natural killer cells" could offer potential against a range of cancers that can evade current treatments, early results from a phase I trial suggest.
Researchers found the new immunotherapy showed signs of effectiveness in a third of patients with a range of advanced cancers that had stopped responding to standard treatment, including bowel and lung cancers.
The immunotherapy, known as AFM24, redirects the body's own natural killer cells and engages them to kill tumor cells, without having to go through a complex process to re-engineer a patient's own cells, as happens with CAR-T cell therapy.
The researchers believe the new treatment has the potential to be safer and less complex than cell therapies like CAR-T, and might also work against a wider range of cancer types.
Ongoing phase I trial
An international team including researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust assessed the new treatment in 24 patients initially in the ongoing phase I trial.
Early findings are being presented at the American Association for Cancer Research (AACR) Annual Meeting 2022.
The Center for Nuclear Receptors and Cell Signaling at the University of Houston has developed a new way to detect very rare and highly heterogeneous circulating tumor cells with high specificity and sensitivity. The UniPro device is reported in the journal Molecular Therapy. UH's Office of Technology Transfer & Innovation is now working with industry partners to establish the best plan to commercialize the technology.
Circulating tumor cells (CTC), which are detached from primary tumors to enter the bloodstream, are particularly hard to detect. Only a few of these rare malignant cells are typically found among millions of white blood cells and billions of red blood cells per milliliter of blood.
Patients with cancers stemming from non-reproductive organs, such as bladder and liver cancer, have striking discrepancies in incidence, progression, response to treatment and survival outcomes depending on their sex. In almost all cases, male patients have worse prognoses and outcomes. This phenomenon has puzzled the scientific community for decades.
A study published today in Science Immunology and led by researchers in the Pelotonia Institute for Immuno-Oncology (PIIO) at The Ohio State University Comprehensive Cancer Center—Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC—James) examined the differences in intratumoral immune responses between male and female cancers of non-reproductive origin
In the face of cancer, oncologists face a dual epidemic of overtreatment and undertreatment. Treating the disease often involves harsh chemotherapies and other interventions with extensive side effects. As a result, clinicians might delay treating a growth that looks harmless until it becomes life threatening and too late to treat. Or, they might overly treat a less aggressive cancer with harsh therapies that cause more harm to the patient than benefit.
Now, two researchers, including Yale's Jason Sheltzer, Ph.D., assistant professor of surgery (oncology), have conducted a study analyzing the molecular features of 33 different human cancers in an effort to find a way to differentiate between non-threatening and aggressive forms of the disease and found surprising results. They published their findings in Cell Reports on March 29.
Scientists have developed a new nanotechnology approach for locating and removing the painful and dangerous lesions associated with endometriosis, a common gynecological condition in women of childbearing age.
The research led by Oleh Taratula of the Oregon State University College of Pharmacy and Ov Slayden of the Oregon National Primate Research Center at Oregon Health & Science University involves magnetic nanoparticles—tiny pieces of matter as small as one-billionth of a meter.
The animal-model study, published today in the journal Small, shows that the iron oxide nanoparticles, injected intravenously, act as a contrast agent—they accumulate in the lesions, making them easier to see by advanced imaging such as MRI.
Mutation of a gene called ARID2 plays a role in increasing the chance that melanoma, a deadly skin cancer, will turn dangerously metastatic, Mount Sinai researchers report.
The findings suggest that patients whose melanoma tumors have an ARID2 mutation may have a more aggressive cancer and may need to be treated differently, according to a study published in Cell Reports in April.
"Our study is the first to characterize the tumor-suppressive functions of ARID2 in melanoma," said the study's lead author Emily Bernstein, Ph.D., Professor of Oncological Sciences at The Tisch Cancer Institute at Mount Sinai. "We modeled ARID2 mutations by removing the ARID2 protein completely from melanoma cells and studied the consequences in the petri dish and in animal models. Recreating actual mutations that patients harbor is challenging, but now possible by genome editing, and would further provide a more accurate model; such studies are ongoing in the lab."
A mutated gene found in more than 20% to 30% of breast cancer recurrences may help tumors become more aggressive and promote metastasis, according to a pair of new studies that uncover mechanisms behind these processes and point to new therapy targets.
"We're excited about this research because it addresses an important clinical problem: A huge number of deaths in breast cancer patients are the result of mutations in estrogen receptor genes," said senior author Steffi Oesterreich, Ph.D., co-leader of the Cancer Biology Program at UPMC Hillman Cancer Center and professor in the University of Pittsburgh School of Medicine Department of Pharmacology & Chemical Biology. "Our study provides a deeper understanding of how these mutations contribute to disease progression and also identifies potential vulnerabilities, which we hope will lead to development of personalized treatment approaches."
A team of researchers affiliated with several institutions in the U.S. and one in the U.K. has developed a new type of Cerenkov luminescence imaging device to help doctors spot cancerous tumors. In their paper published in the journal Nature Biomedical Engineering, the group describes the device, how it works and possible uses for it in clinical settings.
Cerenkov luminescence is a type of electromagnetic radiation where charged particles pass through a dielectric medium at a speed that is faster than regular light in the medium. It is commonly measured by astrophysicists looking at stars and other researchers working in nuclear reactors. Prior research has shown that Cerenkov luminescence can also be generated in the human body as light passes through tissue. It has been suggested that Cerenkov luminescence could be used to help differentiate tumor tissue from normal tissue, and some work has been done to create Cerenkov luminescence imaging (CLI) devices. But to date, such devices have suffered from a variety of issues that have prevented their use in clinical settings. In this new effort, the researchers have designed and built a complete CLI device that has already passed an initial clinical trial.
Checkpoint inhibitors have become important tools in the cancer-fighting arsenal. By blocking proteins that normally restrain the immune response, these drugs can help the immune system destroy cancer cells.
But they don't work in all patients. And now a new study in Nature Immunology led by researchers from Penn's School of Veterinary Medicine suggests a possible reason why: Not only can these drugs encourage the activity of cancer killing T cells, but they can, in some cases, also activate a population of regulatory T cells that serve the opposing function—to rein in that attack.
In the study, immunologists led by Penn Vet professor Christopher Hunter and doctoral student Joseph Perry discovered that blocking the activity of the checkpoint protein PD-L1, which interacts with a T cell receptor PD-1, enhanced the activity of a subset of T cells known as effector regulatory T cells, or effector Tregs. This intervention unexpectedly reduced the ability of mice to control a parasite infection.
The findings reveal a complexity to how the body "regulates the regulators" of the immune system, says Hunter. "Once you have those Tregs to control your T cell response, you also need to control them," he says. "It's like with a car. You have the ignition, the accelerator, and you also need a brake. PD-1 is a brake not only on killer T cells but also on Tregs."
T cells may be best known for their roles in fighting infections and killing cancer cells. But the immune system also has several mechanisms in place to counterbalance those responses to prevent out-of-control inflammation that could damage healthy tissue. Tregs are one aspect of this balancing act.
Although the outlook for people with some types of cancers has improved in the past 20 years, outcomes for patients with uterine and ovarian cancers remain much the same. Patients often have advanced disease before they are diagnosed, and genes that drive tumor formation have proved difficult to target with new treatments.
Now, researchers from the Cancer Dependency Map (DepMap) project at the Broad Institute of MIT and Harvard have identified a hidden vulnerability in ovarian and uterine cancers—as well as a way to exploit it that could inspire new, much-needed drugs for these cancers.
A team led by institute director Todd Golub and DepMap director Francisca Vazquez studied 851 human cancer cell lines to look for genes that uterine and ovarian cancers heavily rely on to survive, known as dependencies. Scientists already knew that uterine and ovarian cancer cells have high levels of a protein called SLC34A2, which imports phosphate into cells. Golub's team disabled another protein in these cells, called XPR1, which exports phosphate out of cells, and found that this killed them. The results, published in Nature Cancer, suggest that the XPR1 gene is a genetic vulnerability in these cells and that phosphate buildup could be toxic to cells. The team adds that disrupting phosphate transport in cancer cells, such as with a protein they used to disable XPR1 in their experiments, could be an effective treatment strategy.
"Patients with ovarian cancer are in desperate need of better therapies, and this XPR1 finding is both surprising and exciting as a starting point for drug discovery," said Golub, who co-led the project. "The challenge now will be to convert this discovery into a therapeutic strategy."
[Northwestern Medicine investigators have discovered a novel signaling pathway activated by interferons, a group of immune system proteins, that suppresses the anti-tumor response of interferons in patients with a particular type of blood cancer, according to findings published in Nature Communications.
Targeting this pathway in combination with interferon therapy may provide a novel approach to improving therapy response and overall patient outcomes.
"Things are not simple with the way the immune system operates. There are different breaks and balances that control the immune response. Here, we defined a unique signaling circuit and identified cellular events that happen when interferon binds to its receptor and starts modifying cellular responses," said Leonidas Platanias, MD, Ph.D., the Jesse, Sara, Andrew, Abigail, Benjamin and Elizabeth Lurie Professor of Oncology, director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and senior author of the study.
Interferons are a group of immune system signaling proteins and are part of the body's first line of defense against disease. When released by host cells, interferons trigger immune cells to fight off viruses and cancer by inhibiting tumor growth, survival, migration and other pro-tumorigenic properties.
An international team of researchers has developed a nanocapsule that is capable of crossing the blood brain barrier (BBB) to carry the CRISPR-Cas9 editing tool to treat a brain tumor. In their paper published in the journal Science Advances, the group describes how they created their capsule and how well it worked when tested in mice with a glioblastoma.
Glioblastomas are notoriously difficult to treat. The tumors appear in the brain and their growth damages tissue. Treatment options include surgical removal, direct injections of therapies meant to kill the cancer cells or inserting CRISPR viruses into the bloodstream. Each of these options has a downside, from damaged brain tissue to ineffectiveness due to difficulties with therapies crossing the BBB. In this new effort, the researchers have tried a new approach, using a nanocapsule to carry the CRISPR-Cas9 editing tool to the brain tumor where it targets a gene that is responsible for the development of new cells—a capsule that is capable of safely crossing the BBB.
A team of researchers from Genetch, Inc., the Howard Hughes Medical Institute and the Peter MacCallum Cancer Center, has found that cancerous tumor cells are able to survive attacks by repairing holes in their membranes caused by a protein released from T cells. In their paper published in the journal Science, the group describes how they used high resolution imaging to learn more about what happens when T cells, known as cytotoxic T lymphocytes (CTLs), attack cancerous tumor cells. Norma Andrews, with University of Maryland, College Park, has published a Perspectives piece in the same journal issue outlining the work done by the team.
Prior research has shown that the way CTLs kill cells infected by a virus or bacteria, and sometimes those that are cancerous, is by glomming onto the cell and then releasing two protein toxins: perforin and granzyme. The first, perforin, eats holes through the cell's membrane. The second then enters the cell through the holes and sets off apoptosis, which is normal programmed cell death. In this new effort, the researchers have learned how cancer cells respond to such an attack.
Metastatic breast cancer cells abuse macrophages, a type of immune cell, to promote the settlement of cancer metastases in the lungs. The reprogrammed macrophages stimulate blood vessel cells to secrete a cocktail of metastasis-promoting proteins that are part of the so-called metastatic niche. This was demonstrated by scientists from the German Cancer Research Center and the Stem Cell Institute HI-STEM in mice that had been transplanted with human breast cancer cells. The work enabled the scientists to identify new targets and develop initial concepts to better restrain the metastatic spread of breast cancer.
Cancer spreads within the body as individual cells detach from the primary tumor and travel to distant body regions via the bloodstream or lymphatic system. Before they can grow into a metastasis at a secondary site, they must communicate with their new environment through a variety of molecular interactions. "In order to settle in this new, hostile milieu, the cancer cells corrupt the microenvironment to support their growth," says Thordur Oskarsson of the German Cancer Research Center (DKFZ) and the stem cell institute HI-STEM. Researchers refer to this as the tumor cells creating a "metastatic niche."
Discovery of MCLA-158, the first clinical candidate screened in organoids targeting cancer stem cells of solid tumors https://medicalxpress.com/news/2022-04- ... eened.html
by Institute for Research in Biomedicine (IRB Barcelona)
Scientists from an international consortium led by Dr. Eduard Batlle, head of the Colorectal Cancer laboratory at IRB Barcelona, ICREA researcher and group leader of CIBER de Cáncer (CIBERONC), together with the Dutch company Merus N.V., reveal the preclinical data that has led to the discovery of MCLA-158 and its mechanism of action on cancer stem cells. Named Petosemtamab, the antibody MCLA-158 prevents the onset of metastasis (that is, the spread of cancer to other vital organs) and slows the growth of primary tumors in experimental models of cancer.
Published today in Nature Cancer, the study also lays the groundwork for the use of organoids in the drug discovery process undertaken by pharmaceutical companies. Organoids are patient-derived samples that can be grown in the laboratory, and they reproduce certain aspects of the tumor compartment. Until now, their usefulness was being explored in personalized cancer medicine—meaning their value in helping physicians make decisions about the best treatment for each patient. However, for the selection of MCLA-158, a biobank of organoids from cancer patients was used for the first time to discriminate which new antibody, among hundreds, was most effective and believed to be most suitable for the majority of patients.
Researchers at Tampere University have successfully developed a novel optical fiber design allowing the generation of rainbow laser light in the molecular fingerprint electromagnetic region. This new optical fiber with a self-cleaned beam can help in developing applications for, for example, pollutant tagging, cancer diagnostics, environmental monitoring, and food control. The finding was published in the journal Nature Communications.
When a high-powered ultrashort pulse of light interacts with a material such as a glass optical fiber, a range of highly nonlinear interactions take place that cause complex changes in both the temporal and spectral properties of the injected light. When taken to the extreme, such interactions can lead to the generation of a rainbow laser of light commonly referred to as a supercontinuum light source. Since its first demonstration in a special type of optical fiber in 2000, supercontinuum laser light has revolutionized many areas of science, ranging from metrology and imaging at unprecedented resolution to ultrabroadband remote sensing and even the detection of exoplanets.
The current bottleneck with current supercontinuum sources, however, is that they are based on optical fibers that support a single transverse intensity profile or mode, which inherently limits their optical power. What's more, conventional optical fibers are made of silica glass with transmission limited to the visible and near-infrared region of the spectrum. Extension of supercontinuum light to other wavelength regimes such as the mid-infrared requires optical fibers made of so-called soft glasses, but these possess a lower damage threshold than silica, limiting even more the power of the supercontinuum beam.
Research from the University of Warwick sheds new light on a key cause of cancer formation during cell division (or mitosis), and points towards potential solutions for preventing it from occurring.
When a cell divides normally, it makes a copy of every chromosome and then shares them equally between the two new cells. This function is carried out by a complex machine in the cell called the mitotic spindle. If something goes wrong at this stage, the two new cells will be aneuploid, meaning that they will not have the correct number of chromosomes and will make mistakes when sharing genetic information.
Cancer cells are aneuploid, so understanding how and why this happens is hugely significant in finding out how the disease originates. Professor Stephen Royle's research team at Warwick Medical School has identified exactly this.