Cancer News and Discussions

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Artificial DNA structures fitted with antibodies may instruct the immune system to target cancerous cells
https://phys.org/news/2023-08-artificia ... erous.html
by Ludwig Maximilian University of Munich

A new study highlights the potential of artificial DNA structures that, when fitted with antibodies, instruct the immune system to specifically target cancerous cells.

Immunotherapy is viewed as an exceptionally promising weapon in the fight against cancer. In essence, the aim is to activate the body's immune system in such a way that it identifies and destroys malignant cells. However, the destruction must be as effective and specific as possible, to avoid damaging healthy cells.

A team of researchers from LMU, the Technical University of Munich (TUM) and Helmholtz Munich have now published a new study in Nature Nanotechnology in which they present a promising method for developing user-defined agents that can do precisely that.

"The centerpiece is a tiny chassis of folded DNA strands that can be specifically fitted with any antibodies," explains Professor Sebastian Kobold, one of the main authors. At Munich University Hospital, his team has investigated the impact of the new substrates both in vitro and in vivo.

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Estrogen-negative cancers respond to anti-estrogenic therapies, study shows
https://medicalxpress.com/news/2023-08- ... apies.html
by Hokkaido University

Anti-estrogenic therapies can suppress the growth of cancer that does not express estrogen receptors; when combined with immune checkpoint inhibitor therapies, they halt tumor progression in mice models.

Estrogen, a group of female hormones, is known to be involved in cancer progression, especially breast cancer. About 75% of breast cancers are estrogen-sensitive: they express the hormone receptor estrogen receptor α (ERα), and estrogen promotes tumor growth. Surprisingly, estrogen has been observed to promote tumor growth in ERα-negative cancers, such as triple-negative breast cancer (TNBC), for reasons that are not fully understood.

A team of researchers from the Institute for Genetic Medicine (IGM) at Hokkaido University has uncovered how estrogen affects the tumor microenvironment and promotes tumor growth in ERα-negative cancers. Their findings were published in the British Journal of Cancer.

"Generally speaking, estrogen directly affects cancer cells to promote cell survival and proliferation, and this has been considered to hold true only for estrogen-sensitive cancers," explains Nabeel Kajihara, lead author of the paper. "Estrogen is also documented to play other roles in the tumor microenvironment, effectively suppressing the immune response and protecting tumors."

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A new targeted treatment shows promise for select patients with stomach cancer
https://medicalxpress.com/news/2023-08- ... ancer.html
by Weill Cornell Medical College

An international phase 3 clinical trial, done in participation with Weill Cornell Medicine and NewYork-Presbyterian, has found that a new targeted treatment called zolbetuximab, given in combination with a standard chemotherapy, extended survival for patients with advanced gastric or gastroesophageal junction cancer that overexpressed a specific biomarker.

Results from the GLOW study, published July 31 in Nature Medicine, together with results from the parallel SPOTLIGHT study that evaluated zolbetuximab with an alternative standard chemotherapy, prompted the United States Food and Drug Administration to grant priority review to the manufacturer's biologic license application and set January 12, 2024, as the target decision date.

If approved, zolbetuximab will be the first targeted therapy in the U.S. for patients with previously untreated advanced gastric or esophageal junction cancer that is human epidermal growth factor receptor 2 (HER2)-negative and overexpresses the protein claudin-18 isoform 2 (CLDN 18.2).

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Common hormone could hold key to treating endometrial cancer
https://medicalxpress.com/news/2023-08- ... ancer.html
by Medical Research Council

New research from QIMR Berghofer has found that the hormone testosterone may play an important role in the development of endometrial cancer.

The discovery raises exciting new possibilities for screening, preventing and fighting this increasingly prevalent disease.

Endometrial cancer is the fourth most common cancer in Australian women and its incidence is rising. Yet treatment options are limited, with a hysterectomy often the first line of defense.

The new study by Associate Professors Tracy O'Mara and Dylan Glubb gives hope that existing hormone therapies may offer another option.

"Everyone has testosterone, but our research suggests that women with higher levels of the hormone are at greater risk of developing endometrial cancer," said A/Prof O'Mara, the senior author on the study.

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Study Shows Topography of the Genome Influences Where Cancer Mutations Thrive
August 24, 2023

Introduction:

(Eurekalert) Researchers at the University of California San Diego have uncovered a connection between the topography of the human genome and the presence of mutations in human cancer. They found that certain regions of the genome, which exhibit unique features, act as hotspots for the accumulation of mutations.

The findings, published recently in Cell Reports, shed light on how the 3D architecture of the human genome may play a role in the development of various forms of cancer.

The human genome is often visualized as the iconic DNA double helix, composed of long sequences of the letters A, C, G and T. “However, the genome is far more than that,” explained study senior author Ludmil Alexandrov, professor of bioengineering and cellular and molecular medicine at UC San Diego. “Like Earth with its diverse landscapes, the genome has a rich topography made up of different structures, shapes and features.”
For example, the genome contains sections where DNA tightly coils, as well as sections where it coils more loosely. Some sections are looped. The genome also possesses various features, such as one called replication timing, where certain regions of the genome are copied early during cell division, while other regions are copied much later.

Alexandrov’s team performed a comprehensive study of how this genomic topography influences where mutations in cancer arise across the human genome. Just as different terrains on Earth foster distinct ecosystems, certain topographic features in the genome seem to provide an environment for specific mutations to thrive.

Read more of the Eurekalert article here: https://www.eurekalert.org/news-releases/999441

Read a technical presentation of the results of the study as published in Cell Reports here: https://www.cell.com/cell-reports/full ... 3)00941-5

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Patients in England will be first to access seven-minute cancer treatment jab
Source: The Guardian

NHS is first health system to offer injection to hundreds of patients which will cut treatment times by up to three quarters.
Patients in England will become the first in the world to benefit from a jab that treats cancer in seven minutes.

The drug, also known as Tecentriq, treats different types of cancer, including lung, breast, liver and bladder cancers. It is given to about 3,600 patients in England each year.

-snip-
The drug is known as a checkpoint inhibitor and works by helping the immune system find and kill cancer cells.

Read more: https://www.theguardian.com/society/202 ... cancer-jab

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Enhancing immune defenses: Researchers unveil the secrets of specialized T cells to conquer tumors
https://medicalxpress.com/news/2023-08- ... lized.html
by University of California - San Diego

Our immune system has an ingenious trick up its sleeve. It remembers past foes, stopping potential sickness in its tracks through a phenomenon known as immunological memory. This is thanks to specialized cells—tissue-resident memory T cells—which reside in vital organs like the small intestine, lungs and other areas. Consider them as frontline guards, stationed exactly where trouble could strike. The endurance of these cells is extraordinary, protecting us from infections we fought decades ago.

Investigations led by University of California San Diego Postdoctoral Scholar Miguel Reina-Campos, Professor Ananda Goldrath and their collaborators at the University of California San Diego and several other institutions have revealed new insights into the metabolism of these specialized immune cells and how they could be enhanced as immune defense weapons against infections and tumors.

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Aggressive Cancer Cells Transformed Into Healthy Cells in Breakthrough
by Michelle Starr
August 29, 2023

Introduction:

(Science Alert) A particularly aggressive form of childhood cancer that forms in muscle tissue might have a new treatment option on the horizon.

Scientists have successfully induced rhabdomyosarcoma cells to transform into normal, healthy muscle cells. It's a breakthrough that could see the development of new therapies for the cruel disease, and it could lead to similar breakthroughs for other types of human cancers.

"The cells literally turn into muscle," says molecular biologist Christopher Vakoc of Cold Spring Harbor Laboratory.

"The tumor loses all cancer attributes. They're switching from a cell that just wants to make more of itself to cells devoted to contraction. Because all its energy and resources are now devoted to contraction, it can't go back to this multiplying state."

Cancer isn't a monolithic thing. It arises when cells from different parts of the body mutate. Rhabdomyosarcoma is a type of cancer that's most often seen in children and adolescents. It usually starts in the skeletal muscle when cells therein mutate and start multiplying and taking over the body.

Read more here: https://www.sciencealert.com/aggressiv ... kthrough

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Aggressive Cancer Cells Transformed Into Healthy Cells in Breakthrough
by Michelle Starr
August 29, 2023

Introduction:

(Science Alert) A particularly aggressive form of childhood cancer that forms in muscle tissue might have a new treatment option on the horizon.

Scientists have successfully induced rhabdomyosarcoma cells to transform into normal, healthy muscle cells. It's a breakthrough that could see the development of new therapies for the cruel disease, and it could lead to similar breakthroughs for other types of human cancers.

"The cells literally turn into muscle," says molecular biologist Christopher Vakoc of Cold Spring Harbor Laboratory.

"The tumor loses all cancer attributes. They're switching from a cell that just wants to make more of itself to cells devoted to contraction. Because all its energy and resources are now devoted to contraction, it can't go back to this multiplying state."

Cancer isn't a monolithic thing. It arises when cells from different parts of the body mutate. Rhabdomyosarcoma is a type of cancer that's most often seen in children and adolescents. It usually starts in the skeletal muscle when cells therein mutate and start multiplying and taking over the body.

Read more here: https://www.sciencealert.com/aggressiv ... kthrough

Very interesting. This is an approach to cancer treatment I've never thought of. I wonder if this concept can be applied to other cancers. This reminds me of an earlier thought I had that cancer might be defeated with clever methods arising from out-of-box thinking.

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Gene therapy for brain tumor shows promising early results in humans
https://medicalxpress.com/news/2023-08- ... early.html
by Anna Megdell, University of Michigan

A new study from the University of Michigan Department of Neurosurgery and Rogel Cancer Center shows promising early results that a therapy combining cell-killing and immune-stimulating drugs are safe and effective in extending survival for patients with gliomas, a highly aggressive form of brain cancer.

The study was published in The Lancet Oncology.

This is a phase 1, first in human trial, and Rogel researchers Pedro Lowenstein M.D., Ph.D., and Maria Castro, Ph.D., lead authors of the study, previously developed and studied the adenoviral mediated gene therapies in their lab. Given gliomas' poor prognosis and limited response to treatments like chemotherapy and radiation, the team looked to using the protein Flt3L to recruit immune cells, typically absent from the brain. These immune cells are required to kick start a more effective cancer immune response.

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Improving CAR T-cell and monoclonal antibody treatment through epitope editing
https://medicalxpress.com/news/2023-09- ... tment.html
by Justin Jackson , Medical Xpress

In a paper, "Epitope editing enables targeted immunotherapy of acute myeloid leukaemia," published in Nature, researchers at the Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, introduce a genetic alteration to donor hematopoietic stem/progenitor cells (HSPCs) that allows them to survive immunotherapy treatment for acute myeloid leukemia (AML).

When the immune system encounters foreign antigens (parts of pathogens or tumors), it tries to identify and neutralize them. Epitopes are the parts of these antigens that the immune system "sees" and recognizes as targets for an immune response.

While chimeric antigen receptor (CAR) T-cells and monoclonal antibodies have shown great promise in treating blood malignancies by targeting antigens on rogue cells, their use with AML is hindered by the lack of tumor-specific markers. This leads to the risk of damaging healthy cells and tissues during treatment.

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Researchers develop novel tumor-targeting nanospheres to improve light-based cancer diagnosis and treatment
https://phys.org/news/2023-09-tumor-tar ... nosis.html
by New York University

In a breakthrough in cancer therapeutics, a team of researchers at the Magzoub Biophysics Lab at NYU Abu Dhabi (NYUAD) has made a significant advance in light-based therapies—biocompatible and biodegradable tumor-targeting nanospheres that combine tumor detection and monitoring with potent, light-triggered cancer therapy to dramatically increase the efficacy of existing light-based approaches.

Non-invasive, light-based therapies, photodynamic therapy (PDT) and photothermal therapy (PTT) have the potential to be safe and effective alternatives to conventional cancer treatments, which are beset by a number of issues, including a range of side-effects and post-treatment complications.

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CRISPR used to 'reprogram' cancer cells into healthy muscle in the lab

Scientists have transformed cancer cells into healthy muscle tissue in the lab using CRISPR gene-editing technology — and they hope new cancer treatments can be built on the back of this experiment. In a study published Aug. 28 in the journal PNAS, researchers found that disabling a particular protein complex in cells of rhabdomyosarcoma (RMS) — a rare cancer in skeletal muscle tissue that mainly affects children under age 10 — in the laboratory causes the tumor cells to turn into healthy muscle cells.

Although the research is still in its early days, this process of "resetting" cancer cells into healthy cells, broadly known as differentiation therapy, has already been tested in other types of cancer, such as bone and blood cancer. Four drugs have been approved by the U.S. Food and Drug Administration (FDA) to treat the latter disease and generally work by inhibiting a specific protein in the cancer cells.

The protein complex pinpointed in the new research could serve as a target for such a therapy, the study authors wrote, and with further development, it could be a promising new treatment option for patients with RMS, which is normally treated with surgery, radiation and chemotherapy.

"This technology can allow you to take any cancer and go hunting for how to cause it to differentiate," or cause it to stop multiplying uncontrollably and turn into normal, noncancerous cells, Christopher Vakoc, lead author and professor at Cold Spring Harbor Laboratory, said in a statement. "This might be a key step toward making differentiation therapy more accessible."

https://www.livescience.com/health/canc ... in-the-lab

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More cases of breast cancer detected with the help of AI
https://medicalxpress.com/news/2023-09- ... er-ai.html
by Karolinska Institutet

One radiologist supported by AI detected more cases of breast cancer in screening mammography than two radiologists working together, reports the ScreenTrustCAD study from Karolinska Institutet in a paper, titled "Artificial intelligence for breast cancer detection in screening mammography: A paired-readers prospective interventional screen positive trial," published in The Lancet Digital Health. The researchers say that AI is now ready to be implemented in breast cancer screening.

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Study reveals proton beam therapy may shorten breast cancer treatment
https://medicalxpress.com/news/2023-09- ... reast.html
by Mayo Clinic

In a randomized trial, published in The Lancet Oncology, Mayo Clinic Comprehensive Cancer Center researchers uncover evidence supporting a shorter treatment time for breast cancer patients.

The study compared two separate dosing schedules of pencil-beam scanning proton therapy, the most advanced type of proton therapy known for its precision in targeting cancer cells while preserving healthy tissue to reduce the risk of side effects.

Survival rates for breast cancer continue to improve due to advances in diagnosis and treatment, leading to increasing emphasis on reducing the long-term toxicity of cancer treatment, including radiotherapy.

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New nanotech weapon takes aim at hard-to-treat breast cancer
https://phys.org/news/2023-09-nanotech- ... reast.html
by Johnny Moseman, Johns Hopkins University

Breast cancer in its various forms affects more than 250,000 Americans a year. One particularly aggressive and hard-to-treat type is triple-negative breast cancer (TNBC), which lacks specific receptors targeted by existing treatments. The rapid growth and metastasis of this cancer also make it challenging to manage, leading to limited therapy options and an often poor prognosis for patients.

A promising new approach that uses minuscule tubes to deliver cancer-fighting drugs directly to the tumor site while preserving healthy cells has been developed by Johns Hopkins engineers. The team's research appeared in Nanoscale.

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Lego-like gene editing tool lets researchers improve cancer immunotherapy
https://medicalxpress.com/news/2023-09- ... erapy.html
by Sarah C. P. Williams, Gladstone Institutes

In recent years, scientists have used gene modification technologies to reprogram immune cells into therapeutics that can attack cancers. But such immunotherapies don't work for all patients or all cancer types, and screening through every possible combination of genetic changes that might improve these reprogrammed immune cells is a daunting and slow task.

Now, scientists at Gladstone Institutes and UC San Francisco (UCSF) have developed a technology that lets them rapidly "snap" together thousands of different combinations of genetic edits to test in immune cells. They used their screening technology, called Modular Pooled Knockin Screening (ModPoKI), to identify a new combination of genes that, when added to immune cells, makes the cells last longer and become more effective at fighting cancers.

"This is a major step forward in our ability to ask questions about how we put pieces of genetic programs together into cells and test how they may be advantageous for patients," says Alex Marson, MD, Ph.D., director of the Gladstone-UCSF Institute of Genomic Immunology and senior author of the new study published in Cell. "I think this is going to accelerate the development of better cellular therapies."

"This study demonstrates the power of using high-throughput genomics to discover and engineer novel molecular programs in cell therapies, and further, to understand the impact of these programs on the T cell state that is required for cancer killing," adds Ansuman Satpathy, MD, Ph.D., affiliate investigator at Gladstone, assistant professor in the Department of Pathology at the Stanford School of Medicine, and co-author of the study.

New research signals a quantum leap for brain tumor treatment
https://phys.org/news/2023-09-quantum-b ... tment.html
by University of Nottingham

Researchers have discovered a new way to target and kill cancer cells in hard-to-treat brain tumors using electrically charged molecules to trigger self-destruction, which could be developed into a spray treatment used during surgery.

A multidisciplinary team of researchers from the University of Nottingham, led by the School of Pharmacy found a new way to harness the extraordinary capabilities of bio-nanoantennae—gold nanoparticles intricately coated with specialized redox active molecules to induce programmed cell death, or apoptosis, in cancer cells on electrical stimulation. The research has been published in Nature Nanotechnology.

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Researchers discover possible new treatment for triple-negative breast cancer
https://medicalxpress.com/news/2023-09- ... ancer.html
by The Wistar Institute

Zachary Schug, Ph.D., assistant professor in the Molecular and Cellular Oncogenesis Program of the Ellen and Ronald Caplan Cancer Center at The Wistar Institute, has published a new paper in the journal Nature Cancer. Schug's paper, titled "Acetate acts as a metabolic immunomodulator by bolstering T-cell effector function and potentiating antitumor immunity in breast cancer," demonstrates a double-acting mechanism for fighting a particularly aggressive, difficult-to-treat form of breast cancer. Schug's research shows how silencing a certain gene, ACSS2, may improve existing treatments for patients.

Triple-negative breast cancer, or TNBC, affects 10–15% of patients with breast cancer in the US. TNBC is called "triple-negative" because the cancer lacks an estrogen receptor, a progesterone receptor, and a HER2 (human epidermal growth factor) receptor. The absence of any of these receptors—receptors that when present in other forms of breast cancer, can be effectively targeted during treatment—makes treating TNBC quite difficult, and patients with TNBC have limited treatment options.

TNBC's notorious aggression makes the technical challenge of finding a reliably effective treatment target all the more serious: compared to other breast cancers, TNBC grows faster and resists treatment more stubbornly. All these factors contribute to the fact that TNBC patients suffer from worse prognoses.

But Schug and co-authors have demonstrated the efficacy of a double-acting concept: Silencing the gene ACSS2 impairs TNBC metabolism while simultaneously boosting the immune system's ability to fight it. ACSS2 regulates acetate, a nutrient that cancer cells—and TNBC cells in particular—take advantage of to grow and spread. Schug and his team used two methods to de-activate ACSS2: CRISPR-Cas9 gene editing, and the compound VY-3-135, a potent ACSS2 inhibitor identified by Schug and his colleagues in 2021.

The researchers found that targeting ACSS2 in this preclinical study not only hampered this aggressive cancer's ability to metabolize acetate and grow, it also triggered the immune system to recognize and attack the cancer. Because cancer cells with inhibited ACSS2 can't process acetate very well, the tumor region becomes bathed in acetate, which alerts the immune system of something amiss.

This process of guiding the immune system to the cancer—called "immunosensitization"—has confounded other TNBC researchers. But Schug's approach showed that ACSS2 inhibition immunosensitized against TNBC so well that tumor growth was drastically reduced, even to the point of wiping out the cancer completely in some experiments.