Cancer News and Discussions

weatheriscool
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Whole exome sequencing predicts whether patients respond to cancer immunotherapy
https://medicalxpress.com/news/2022-07- ... erapy.html
by New York University
Immunotherapies, such as immune checkpoint inhibitors, have transformed the treatment of advanced stage cancers. Unlike chemotherapies that kill cancer cells, these drugs help the body's immune system to find and destroy cancer cells themselves. Unfortunately, only a subset of patients responds long-term to immune checkpoint inhibitors—and these treatments can come at a high cost and with side effects.

Researchers have developed a two-step approach using whole exome sequencing to zero in on genes and pathways that predict whether cancer patients will respond to immunotherapy. The study, published in Nature Communications and conducted by researchers at New York University, Weill Cornell Medicine, and the New York Genome Center, illustrates how the use of whole exome sequencing can better predict treatment response than current laboratory tests.
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Malignant or benign? Quick and accurate diagnosis with artificial tactile neurons
https://medicalxpress.com/news/2022-07- ... nosis.html
by National Research Council of Science & Technology

The stiffness levels and distributions of biological materials reflect disease-related information, from cells to tissues. For example, malignant breast tumors are usually stiffer and have a more irregular shape than benign breast tumors. Ultrasound elastography can non-invasively determine the degree and shape of the tissue stiffness and is used for diagnosing breast cancer due to its low cost. However, the opinion of an experienced expert is essential for interpreting ultrasound elastography images, but different experts differ in accuracy.

Teams led by Dr. Hyunjung Yi and Suyoun Lee have developed a simple but highly accurate disease diagnosis technology by combining tactile neuron devices with artificial neural network learning methods. Unlike the previously reported artificial tactile neuron devices, this tactile neuron device can determine the stiffness of objects. Their results were published in Advanced Materials.

Neuromorphic technology is a research field that aims to emulate the human brain's information processing method, which is capable of high-level functions while consuming a small amount of energy using electronic circuits. It is gaining attention as a new data processing technology useful for AI, IoT and autonomous driving, requiring the real-time processing of complex and vast information.
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Primary cilia in medulloblastoma: Mechanisms provide treatment opportunity

by St. Jude Children's Research Hospital
https://medicalxpress.com/news/2022-07- ... tment.html
Scientists at St. Jude Children's Research Hospital have identified how an appendage on the surface of cells, called the primary cilium, contributes to certain types of medulloblastoma. The study has implications for drug development. The research appeared today in Genes & Development.

Medulloblastoma is the most common malignant childhood brain tumor. There are four subgroups of medulloblastoma: SHH, WNT, group 3 and group 4. SHH and WNT tumors are driven by mutations in their namesake signaling pathways, but group 3 and group 4 have no common driver mutations other than MYC amplification in about 17% of group 3 medulloblastoma. Each group has distinct molecular, pathologic and clinical features.

The primary cilium is a signaling appendage projecting from the surface of cells. It helps control the cell's function and behavior. The presence or absence of primary cilia is a notable feature in different diseases including cancer. How this appendage contributes to cancer development and growth is understudied in most tumors.

"Primary cilia are structures that were discovered over 100 years ago, but we are still coming to appreciate the role that they play in human health and disease," said corresponding author Young-Goo Han, Ph.D., St. Jude Department of Developmental Neurobiology.
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Targeting bicarbonate in cancer
https://medicalxpress.com/news/2022-07- ... ancer.html
by Will Doss, Northwestern University
Bicarbonate ions are required for cell growth in some cancers, according to a Northwestern Medicine study published in the journal Molecular Cell.

Inhibition of a key bicarbonate transporter could lead to a cancer therapy with fewer side effects compared to currently available treatments, according to Issam Ben-Sahra, Ph.D., assistant professor of Biochemistry and Molecular Genetics and senior author of the study.

"This transporter is very important in cancer but less so in normal cells," said Ben-Sahra, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. "It could be a very interesting target."

Eunus Ali, Ph.D., a postdoctoral fellow in the Ben-Sahra laboratory, was lead author of the study.

Bicarbonate ions are present in high concentration throughout the blood and are important for maintaining pH in cells. The ions are also used to make purine and pyrimidines, essential building blocks of nucleotide molecules.

In previously published studies, the Ben-Sahra laboratory found that many cancers upregulate nucleotide biosynthesis through the mTORC1 pathway, helping fuel cell growth and cancer proliferation. However, whether bicarbonate is controlled and utilized in this pathway was unknown, according to Ben-Sahra.
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Scientists discover genes that affect risk of developing pre-leukemia
https://medicalxpress.com/news/2022-07- ... kemia.html
by University of Bristol

The discovery of 14 inherited genetic changes which significantly increase the risk of a person developing a symptomless blood disorder associated with the onset of some types of cancer and heart disease is published today in Nature Genetics. The finding, made in one of the largest studies of its kind through genetic data analysis on 421,738 people, could pave the way for potential new approaches for the prevention and early detection of cancers including leukemia.

Led by scientists from the Universities of Bristol and Cambridge, the Wellcome Sanger Institute, the Health Research Institute of Asturias in Spain, and AstraZeneca, the study reveals that specific inherited genetic changes affect the likelihood of developing 'clonal haematopoiesis', a common condition characterized by the development of expanding clones of multiplying blood cells in the body, driven by mutations in their DNA.

Although symptomless, the disorder becomes ubiquitous with age and is a risk factor for developing blood cancer and other age-related diseases. Its onset is a result of genetic changes in our blood-making cells.
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Bacteria-based biohybrid microrobots on a mission to one day battle cancer
https://phys.org/news/2022-07-bacteria- ... n-day.html
by Max Planck Society
A team of scientists in the Physical Intelligence Department at the Max Planck Institute for Intelligent Systems have combined robotics with biology by equipping E. coli bacteria with artificial components to construct biohybrid microrobots. First, as can be seen in Figure 1, the team attached several nanoliposomes to each bacterium. On their outer circle, these spherical-shaped carriers enclose a material (ICG, green particles) that melts when illuminated by near infrared light. Further towards the middle, inside the aqueous core, the liposomes encapsulate water soluble chemotherapeutic drug molecules (DOX).

The second component the researchers attached to the bacterium is magnetic nanoparticles. When exposed to a magnetic field, the iron oxide particles serve as an on-top booster to this already highly motile microorganism. In this way, it is easier to control the swimming of bacteria—an improved design toward an in vivo application. Meanwhile, the rope binding the liposomes and magnetic particles to the bacterium is a very stable and hard to break streptavidin and biotin complex, which was developed a few years prior and reported in a Nature article, and comes in useful when constructing biohybrid microrobots.
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Strengthening the immune response to cancer
https://medicalxpress.com/news/2022-07- ... ancer.html
by Max Delbrück Center for Molecular Medicine

For patients with lymphoma, multiple myeloma, or certain types of leukemia, treatment with chimeric antigen receptor T cells (CAR T cells) is sometimes the last chance of overcoming the cancer. The treatment involves taking T cells from the patient's blood and adding artificial receptors—the CARs—to them in the lab. As the guards of our immune system, T cells are on permanent patrol in our blood vessels and tissues, where they hunt down foreign structures. Equipped with CARs, T cells can also detect very specific surface structures on cancer cells. Once the CAR T cells are returned to the patient by infusion, they circulate in the body as a kind of living drug that can bind to very specific tumor cells and destroy them.

The engineered immune cells remain in the body permanently and multiply. If the cancer flares up again, they'll go back into action. That's the theory, at least. But in practice, many patients still relapse. This is because the tumor cells can outwit the CAR T cells by producing more of the protein EBAG9—and by causing the T cells to produce more of it, too. In T cells, EBAG9 inhibits the release of cytotoxic enzymes, which slows the desired immune response.

A month earlier, a team led by last authors Dr. Armin Rehm and Dr. Uta Höpken from the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) showed in the journal JCI Insight that shutting down the EBAG9 gene in mice led to a sustained increase in the immune response to cancer. The mice also developed more T memory cells. These cells are part of our immunological memory, which allows our immune system to respond better to a cancer antigen after encountering it previously.
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Scientists develop new biomimetic formulation for treating glioblastoma
https://phys.org/news/2022-07-scientist ... stoma.html
by Li Yuan, Chinese Academy of Sciences
Glioblastoma multiforme (GBM) is an aggressive brain cancer with a poor prognosis and few treatment options. New and effective approaches for GBM treatment are therefore urgently needed.

Based on observation of elevated lactate in resected GBM, researchers from the Institute of Process Engineering (IPE) of the Chinese Academy of Sciences and Shenzhen Second People's Hospital have developed a biomimetic formulation using targeted delivery agents for lactate metabolism-based synergistic therapy against GBM.

The study was published in Nature Communications on July 21.

Targeting lactate metabolism is an attractive tumor therapeutic strategy. However, there are no reports that directly harness lactate metabolism for GBM treatments. One limitation is the existence of the blood-brain barrier, which prevents most drug molecules (including those interfering with lactate metabolism) from reaching the brain.
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Scientists identify a key gene that is turned on in most cancer types

by Alex Viveros, Broad Institute of MIT and Harvard
https://medicalxpress.com/news/2022-07- ... ancer.html
Physician-scientists at the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute have discovered that a gene called FOXR2 that is normally turned off in most tissues in the body is activated in at least 70% of cancer types and 8% of all individual tumors.

Their study, recently published in Cancer Research, may help scientists better understand how a variety of cancers develop. The research team has already started working with chemists and structural biologists to figure out how to target this gene with possible new treatments.

"The fact that this gene is normally switched off in most tissues means that we might be able to target it in a way that doesn't cause a lot of side effects," said senior author Pratiti Bandopadhayay, an associate member at the Broad and a pediatric neuro-oncologist at Dana-Farber.

Finding FOXR2

Jessica Tsai, a pediatric oncologist at Dana-Farber, a postdoctoral fellow in Bandopadhayay's lab, and first author of the paper was analyzing genome sequences of a kind of pediatric brain cancer called diffuse midline gliomas—fatal tumors in the middle of the brain—when she and her team found, to their surprise, that many of the cancers showed abnormal expression of FOXR2. This gene encodes a transcription factor, is located on the X chromosome, and is normally expressed only in the testis.

"Really, any normal tissue other than testis shouldn't have any FOXR2 expression, so that finding stood out to us initially," said Tsai.
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Investigational blood test can detect multiple signs of brain cancer to improve diagnosis and monitoring
https://medicalxpress.com/news/2022-07- ... nosis.html
by Katie Marquedant, Massachusetts General Hospital
Researchers at Massachusetts General Hospital (MGH) who previously developed a blood test for mutations in a gene linked to gliomas, the most common type of adult brain tumors, have now applied their technology to detect additional mutations, in this case in the gene that codes for epidermal growth factor receptor (EGFR).

The advance, which is described in a study published in Clinical Cancer Research, provides clinicians with a powerful tool to detect the presence of gliomas, characterize the tumors, and monitor their status after treatment.

The team's test is a form of liquid biopsy that detects pieces of tumor cells' genetic material—called mRNA—that are circulating in the blood.

A previous study first reported the technique, a highly optimized novel digital droplet polymerase chain reaction (ddPCR) blood test, for accurately detecting and monitoring the presence of two mutations of the gene TERT, which is commonly mutated in glioma tumors.

After further tailoring their technique to detect mRNA produced from a mutated EGFR gene called EGFRvIII that is often present in especially aggressive gliomas, the investigators determined the prevalence of EGFRvIII mRNA in glioma tumor tissue from 37 tumor tissue samples, and they tested their blood test in plasma samples from 30 patients with gliomas with tissue-confirmed EGFRvIII, 10 patients with gliomas with no EGFR mutations, and 14 healthy controls.

The team reported that the blood test had an overall sensitivity (ability to detect the presence of EGFRvIII) of 72.8% and a specificity (ability to detect the absence of EGFRvIII) of 97.7%.
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