Cancer News and Discussions

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MIT Develops Nanoparticles That Cross the Blood-Brain Barrier To Treat Cancer Tumors

https://scitechdaily.com/mit-develops-n ... er-tumors/
By Anne Trafton, Massachusetts Institute of Technology June 24, 2022
Tested using a new brain tissue model, the tiny particles may be able to deliver chemotherapy drugs for glioblastoma, a fast-growing and aggressive type of cancer.

Currently, there are very few good treatment options for glioblastoma, an aggressive type of brain cancer with a high fatality rate. One reason that the disease is so difficult to treat is that most chemotherapy drugs can’t penetrate the blood vessels that surround the brain.

A team of scientists at MIT is now developing drug-carrying nanoparticles that appear to get into the brain more efficiently than drugs given on their own. Using a human tissue model they designed, which accurately replicates the blood-brain barrier, the scientists showed that the particles could get into tumors and kill glioblastoma cells.

In the past, many potential glioblastoma treatments have shown success in animal models but then ended up failing in clinical trials. This suggests that a better kind of modeling is needed, says Joelle Straehla, the Charles W. and Jennifer C. Johnson Clinical Investigator at MIT’s Koch Institute for Integrative Cancer Research, an instructor at Harvard Medical School, and a pediatric oncologist at Dana-Farber Cancer Institute.

“We are hoping that by testing these nanoparticles in a much more realistic model, we can cut out a lot of the time and energy that’s wasted trying things in the clinic that don’t work,” she says. “Unfortunately, for this type of brain tumor, there have been hundreds of trials that have had negative results.”
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Lipid nanoparticles carry gene-editing cancer drugs past tumor defenses
https://phys.org/news/2022-06-lipid-nan ... drugs.html
by UT Southwestern Medical Center
As they grow, solid tumors surround themselves with a thick, hard-to-penetrate wall of molecular defenses. Getting drugs past that barricade is notoriously difficult. Now, scientists at UT Southwestern have developed nanoparticles that can break down the physical barriers around tumors to reach cancer cells. Once inside, the nanoparticles release their payload: a gene editing system that alters DNA inside the tumor, blocking its growth and activating the immune system.

The new nanoparticles, described in Nature Nanotechnology, effectively stopped the growth and spread of ovarian and liver tumors in mice. The system offers a new path forward for the use of the gene editing tool known as CRISPR-Cas9 in cancer treatment, said study leader Daniel Siegwart, Ph.D., Associate Professor of Biochemistry at UT Southwestern.

"Although CRISPR offers a new approach for treating cancer, the technology has been severely hindered by the low efficiency of delivering payloads into tumors," said Dr. Siegwart, a member of the Harold C. Simmons Comprehensive Cancer Center.

In recent years, CRISPR-Cas9 technology has given researchers a way to selectively edit the DNA inside living cells. While the gene editing system offers the potential to alter genes that are driving cancer growth, delivering CRISPR-Cas9 to solid tumors has been challenging.

For more than a decade, Dr. Siegwart and his colleagues have been studying and designing lipid nanoparticles (LNPs), small spheres of fatty molecules which can carry molecular cargo (including recent mRNA COVID-19 vaccines) into the human body. In 2020, Dr. Siegwart's group showed how to direct nanoparticles to specific tissues, which had been a challenge limiting the field.
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Dynamic cells linked to brain tumor growth and recurrence
https://medicalxpress.com/news/2022-06- ... tumor.html
by Anna Megdell, University of Michigan
Tumors are made up of many types of cells, both cancerous and benign. The specific complexity of the cells inside brain tumors has been a trademark of the disease, one that makes treatment extremely difficult. While scientists have long known about the variety of cells within a brain tumor, the ways these tumors grow has relied on the understanding that the cells are static, unmoving and relatively fixed.

But researchers at the University of Michigan Rogel Cancer Center have discovered that these aggressive tumors contain highly active cells that move throughout tissue in complicated patterns. What's more, the accumulations of these elongated, spindle-like cells found throughout the tumor, coined 'oncostreams,' serve as the basis for cancerous cells' behavior, determining how tumors grow and invade normal tissue.

Pedro Lowenstein, M.D., Ph.D., Richard C. Schneider Collegiate Professor of Neurosurgery and lead author of this study in Nature Communications, says this organized growth is what makes brain tumors so relentless.
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New health research suggests novel combination therapy for triple-negative breast cancer
https://medicalxpress.com/news/2022-06- ... reast.html
by Louisiana State University
Three-dimensional culture of human breast cancer cells, with DNA stained blue and a protein in the cell surface membrane stained green. Image created in 2014 by Tom Misteli, Ph.D., and Karen Meaburn, Ph.D. at the NIH IRP.

Research led by Suresh Alahari, Ph.D., Professor of Biochemistry at LSU Health New Orleans schools of Medicine and Graduate Studies, suggests a combination of drugs already approved by the FDA for other cancers may be effective in treating chemo-resistant triple-negative breast cancer. The results are published in Molecular Cancer.

Triple-negative breast cancer (TNBC) tumors lack estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). A subtype representing 12-55% of triple-negative breast cancer tumors has androgen receptors (AR). Since androgen receptors stimulate tumor cell progression in estrogen receptor-negative breast cancers, they have become a target of triple-negative breast cancer therapy. As well, since a substantial number of patients with triple-negative breast cancer develop resistance to paclitaxel, the FDA-approved chemotherapeutic agent for triple-negative breast cancer, new therapeutic approaches are needed.

Working in a mouse model and tissue from patients with triple-negative breast cancer, the research team screened 133 FDA-approved drugs that have a therapeutic effect against androgen receptor cells. They found that ceritinib, an FDA-approved drug for lung cancers, efficiently inhibited the growth of androgen receptor triple-negative breast cancer cells. To improve the response, they also selected enzalutamide, an FDA-approved androgen receptor antagonist for prostate cancer treatment.
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Scientists unravel the key to colon cancer relapse after chemotherapy
https://medicalxpress.com/news/2022-07- ... ancer.html
by University of Barcelona
Approximately 1 in 25 people will develop colon cancer during their lifetime and nearly 2 million cases new cases are diagnosed worldwide each year. Chemotherapy is commonly used to treat colon cancer. While this treatment is initially effective in most cases, many patients relapse after treatment.

Led by Dr. Eduard Batlle, ICREA researcher and head of the Colorectal Cancer Laboratory at IRB Barcelona, this study reveals that some tumor cells remain in a latent state and, after chemotherapy, they are reactivated, thus causing relapse. Their study is published in Nature Cancer.

In short, scientists have discovered that tumor stem cells with Mex3a protein activity remain in a state of latency that confers resistance to chemotherapy. Due to the action of the drugs used in this treatment, these cells adopt a state similar to the embryonic one, and sometime after chemotherapy, when the environment is more favorable, they are reactivated to regenerate the tumor in all its complexity. These persistent cells are responsible for cancer relapse after treatment.

"Chemotherapy is effective and kills most of the tumor cells but not all of them. Our discovery reveals the identity of a group of persistent cells that are resistant to chemotherapy go on to regenerate the tumor after treatment. Our work paves the way for the development of drugs to eliminate these cells, which would make chemotherapy more effective and improve survival rates," explains Dr. Batlle, also a group leader in the Cancer CIBER (CIBERONC).
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Researchers shed light on importance of ecological cellular interactions in targeted therapy resistance in lung cancer
https://medicalxpress.com/news/2022-07- ... erapy.html
by Cleveland Clinic
New Cleveland Clinic research has uncovered key information about cellular interaction between tumor cells and normal tissue, providing better understanding of how therapeutic resistance develops.

"In the study of drug resistance, researchers often try to understand the fitness of cells that have specific mutations in the presence of a drug in a laboratory setting," explained Jacob Scott, M.D., D.Phil., radiation oncologist and head of Cleveland Clinic's Theory Division in the Lerner Research Institute Department of Translational Hematology and Oncology Research. "But the reality is more complex, because tumor cells don't exist in a vacuum; instead, they co-exist in a complex, heterogeneous mixture of other tumor cells and normal tissues—an interacting ecology."

With approximately 90% of cancer deaths attributed to treatment-resistant disease, these cellular interactions, also known as "evolutionary games," have high stakes.

In their latest study published DATE in Science Advances, Dr. Scott and his collaborators used an assay they previously developed to directly measure those interactions in a simplified tumor environment consisting of drug-resistant non-small cell lung cancer cells and drug-sensitive precursor (ancestor) cells.
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New classification system proposed for colorectal cancer to guide treatment and clinical trials
https://medicalxpress.com/news/2022-07- ... nical.html
by SingHealth
A team of clinician-scientists and scientists, led by the National Cancer Centre Singapore (NCCS) and A*STAR's Genome Institute of Singapore (GIS) together with collaborators in Europe and South Korea, used single cell techniques to uncover a central dichotomy for colorectal cancer cells, leading to a proposed update of the classification system for the disease. These findings, published in Nature Genetics on 30 June 2022, have implications for drug development and treatment approaches in colorectal cancer.

In Singapore and worldwide, colorectal cancer is one of the most common cancers and the second-leading cause of cancer death. As it is a heterogeneous disease with substantial biological and clinical differences amongst patients, treating colorectal cancer and prescribing individualized treatment for patients directed by the biology of their disease is a challenge. In 2015, clinicians and scientists classified colorectal cancer based on genes expressed by the tumor (transcriptomics) leading to the 2015 international consensus molecular subtype (CMS1-4) classification, that is to date, the most robust and widely used transcriptomic system. However, the CMS classification relied on transcriptomic analysis of the entire tumor which meant that the individual differences from cancer cells and other stromal cells (e.g. immune, fibroblast & blood vessel cells) were obscured and could not be distinguished.
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Study reveals how gastric cancer forms, suggests preventive treatment
https://medicalxpress.com/news/2022-07- ... tment.html
by Vanderbilt University

A recently published study reveals new insights into how gastric cancer develops and suggests a preventive treatment.

Eunyoung Choi, Ph.D., assistant professor of Surgery, and colleagues identified for the first time that Trop2+/CD133+/CD166+ dysplastic stem cells are a key source of clonal evolution of dysplasia to multiple types of gastric cancer. Their investigation further showed that pyrvinium, a commonly prescribed treatment for intestinal pinworms, blocked regeneration of dysplastic stem cells by controlling the CK1a signaling protein in mouse models and in human organoids.

Their findings were published online June 11 in Gastroenterology.

"The dysplastic stem cells that we identified are de novo stem cells first present during carcinogenic transition of pre-cancerous metaplasia to dysplasia in both mouse and human stomachs. Our study also demonstrated cell fate dynamics and evolutionary process of dysplastic stem cells as a single-type of non-cancerous stem cells in dysplasia and provided a clue, which explains full spectrum of a carcinogenic cascade, normal-metaplasia-dysplasia-adenocarcinoma, during gastric cancer development," said Choi, the study's corresponding author.
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Structure of antibodies could be key to more effective cancer treatments
https://medicalxpress.com/news/2022-07- ... ments.html
by University of Southampton
Researchers at the University of Southampton have gained unprecedented new insight into the key properties of an antibody needed to fight off cancer.

The interdisciplinary study, published in Science Immunology, revealed how changing the flexibility of the antibody could stimulate a stronger immune response.

The findings have enabled the Southampton team to design antibodies to activate important receptors on immune cells to "fire them up" and deliver more powerful anti-cancer effects.

The scientists believe their findings could pave the way to improve antibody drugs that target cancer as well as other autoimmune diseases.

In the study, the team investigated antibody drugs targeting the receptor CD40 for cancer treatment. Clinical development has been hampered by a lack of understanding of how to stimulate the receptors to the right level. The problem being that if antibodies are too active they can become toxic.
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New gene profiling technology reveals melanoma biomarkers
https://medicalxpress.com/news/2022-07- ... anoma.html
by UC Davis

A new UC Davis-led study sheds light on cell type-specific biomarkers, or signs, of melanoma. The research was recently published in the Journal of Investigative Dermatology.

Melanoma, the deadliest of the common skin cancers, is curable with early diagnosis and treatment. However, diagnosing melanoma clinically and under the microscope can be complicated by what are called melanocytic nevi—otherwise known as birth marks or moles that are non-cancerous. The development of melanoma is a multi-step process where "melanocytes," or the cells in the skin that contain melanin, mutate and proliferate. Properly identifying melanoma at an early stage is critical for improved survival.

"The biomarkers of early melanoma evolution and their origin within the tumor and its microenvironment are a potential key to early diagnosis of melanoma," said corresponding author of the study Maija Kiuru, associate professor of clinical dermatology and pathology at UC Davis Health. "To unravel the mystery, we used high-plex spatial RNA profiling to capture distinct gene expression patterns across cell types during melanoma development. This approach allows studying the expression of hundreds or thousands of genes without disrupting the native architecture of the tumor."
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