Cancer News and Discussions

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Every Single Patient in This Small Experimental Drug Trial Saw Their Cancer Disappear
PETER DOCKRILL
6 JUNE 2022
https://phys.org/news/2022-06-nasa-euro ... -main.html

In what appears to be a very promising breakthrough for the treatment of rectal cancer, a small drug trial conducted in the US found every patient treated in the experiment had their cancer successfully go into remission.

The medication given, called dostarlimab and sold under the brand name Jemperli, is an immunotherapy drug used in the treatment of endometrial cancer, but this was the first clinical investigation of whether it was also effective against rectal cancer tumors.

The early results reported so far suggest it is surprisingly effective, with the research team saying the successful cancer remission seen in every trial patient may be unprecedented for a cancer drug intervention.

"I believe this is the first time this has happened in the history of cancer," medical oncologist Luis Diaz Jr. from Memorial Sloan Kettering Cancer Center (MSK), the senior author of a new paper reporting the results, told The New York Times.

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Study identifies receptor that could alleviate need for chemo, radiation pre-T cell therapy
https://medicalxpress.com/news/2022-06- ... -cell.html
by University of California, Los Angeles

Before a patient can undergo T cell therapy designed to target cancerous tumors, the patient's entire immune system must be destroyed with chemotherapy or radiation. The toxic side effects are well known, including nausea, extreme fatigue and hair loss.

Now a research team, led by UCLA's Anusha Kalbasi, MD, in collaboration with scientists from Stanford and the University of Pennsylvania, has shown that a synthetic IL-9 receptor allows those cancer-fighting T cells to do their work without the need for chemo or radiation. T cells engineered with the synthetic IL-9 receptor, designed in the laboratory of Christopher Garcia, Ph.D., at Stanford, were potent against tumors in mice, as published Wednesday in Nature.

"When T cells are signaling through the synthetic IL-9 receptor, they gain new functions that help them not only outcompete the existing immune system but also kill cancer cells more efficiently," Kalbasi said. "I have a patient right now struggling through toxic chemotherapy just to wipe out his existing immune system so T cell therapy can have a fighting chance. But with this technology you might give T cell therapy without having to wipe out the immune system beforehand."

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Researchers find that aspirin alters colorectal cancer evolution
https://medicalxpress.com/news/2022-06- ... ution.html
by University of California, Irvine

Cancer starts when cells start dividing uncontrollably. Scientists have known that taking aspirin can help protect against the development of colorectal cancer—cancer afflicting the colon or rectum—but the exact reason aspirin has this effect has been mostly a mystery.

In a new study published in the journal eLife, researchers at the University of California, Irvine reveal for the first time that aspirin changes the way colorectal cancer cell populations evolve over time, making them less able to survive and proliferate.

"We asked what aspirin does to the Darwinian evolution of cells," said co-author Dominik Wodarz, professor of population health and disease prevention at the UCI Program in Public Health. "Cancer arises because cells evolve from a healthy state toward a pathogenic state where the cells divide without stopping. This happens when cells acquire a number of mutations, and these mutations are selected for. We found that aspirin affects these evolutionary processes and slows them down."

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Scientists create nanoparticle that helps fight solid tumors
https://medicalxpress.com/news/2022-06- ... umors.html
by Wake Forest University Baptist Medical Center

Researchers from Wake Forest University School of Medicine have discovered a possible new approach in treating solid tumors through the creation of a novel nanoparticle. Solid tumors are found in cancers such as breast, head and neck, and colon cancer.

In the study, Xin Ming, Ph.D., associate professor of cancer biology at Wake Forest University School of Medicine, and his team used a nanoparticle to deliver a small molecule called ARL67156 to promote an anti-tumor immune response in mouse models of colon, head and neck, and metastatic breast cancer, resulting in increased survival.

The study is published online in the journal Science Translational Medicine.

Immunotherapy has transformed cancer treatment, but unfortunately, only about 20% of patients respond to treatment.

"Most solid tumors have a poor microenvironment that can make them unresponsive to conventional cancer therapeutics, including immunotherapy," Ming said. "But this study demonstrates that nanoparticle therapeutics are promising."

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Deep learning empowers discovery of new genetic mutation in cancer
https://medicalxpress.com/news/2022-06- ... ation.html
by Will Doss, Northwestern University

A machine-learning model has helped scientists discover hundreds of genetic mutations in cancer that are undetectable by current genome sequencing, according to a study published in the journal Science Advances.

These findings provide new targets for cancer classification and potential therapy, according to Feng Yue, Ph.D., the Duane and Susan Burnham Professor of Molecular Medicine and senior author of the study.

"Our work identified many previously unknown fusion events in cancer genomes and also captured novel regulatory mechanism for known oncogenes," said Yue, who is also an associate professor of Biochemistry and Molecular Genetics, of Pathology and director of the Center for Cancer Genomics at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

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TCF-1 protein plays essential role in breaking down barriers as T cells form

by Perelman School of Medicine at the University of Pennsylvania
https://medicalxpress.com/news/2022-06- ... riers.html

The protein TCF-1 enables various parts of otherwise insulated DNA segments to intermingle in a way that is required for the development of T cells—a key element of the body's immune system—and the role this protein plays in T cell creation could shed new light on immunotherapy approaches, according to a new study by researchers at the Perelman School of Medicine at the University of Pennsylvania. The findings are published today in Nature Immunology.

Mammalian DNA is folded in 3D structures that create what one can think of as different neighborhoods in the genome. These neighborhoods, formally called topologically associating domains, or TADs, are sections of DNA that are insulated from other neighborhoods in order to control the expression of different genes. Sometimes, these neighborhoods need to intermingle because a piece of DNA in one neighborhood may be required to control and develop a unique set of genes in another.

By studying the mechanics of the protein TCF-1 and how it reconfigures the genome, a research team led by Golnaz Vahedi, Ph.D., an associate professor of Genetics and a member of the Penn Institute for Immunology and Penn Epigenetics Institute, discovered that the TCF-1 protein has a unique ability to enable plasticity in cells across neighborhoods during the development of T cells.

"These domains, or insulated neighborhoods, are like stickers for social distancing," Vahedi said. "They essentially say, 'Stay away—keep a certain distance apart.' But what this protein does is to remove these stickers and say, 'You can now actually intermingle.' It disrupts the spatial distancing."

Using various basic science experiments, the researchers saw that TCF-1, along with the protein CTCF, targets boundaries of insulated neighborhoods when T cells are developing, thereby weakening the insulation and minimizing the distance between these adjacent neighborhoods that were previously blocked off. The co-binding of TCF-1 with CTCF increases interactions across neighborhoods as T cells mature, indicating that TCF-1 plays an essential role in the development and maturation of T cells, which are a central component of immunotherapies that aim to manipulate T cells as drugs to proliferate and kill cancer cells.

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Biomarkers found that could be drug targets against a deadly form of brain cancer

by Georgetown University Medical Center
https://medicalxpress.com/news/2022-06- ... ancer.html

Biomarkers that could be targets for novel drugs to treat glioblastoma brain tumors have been identified by investigators at Georgetown Lombardi Comprehensive Cancer Center, providing hope for a cancer that is highly lethal.

Currently, the drug most often used to treat glioblastoma, temozolomide, is uniquely able to cross the blood/brain barrier to attack the tumor but resistance develops rapidly, and many patients do not survive for more than a year after diagnosis. This new finding provides early evidence that there may be a benefit in targeting specific alterations in cancer cells with newer agents once a patient's tumor becomes resistant to temozolomide.

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Pushing T cells down 'memory lane' may improve cancer therapy
https://medicalxpress.com/news/2022-06- ... erapy.html
by St. Jude Children's Research Hospital

Scientists at St. Jude Children's Research Hospital identified a molecular mechanism that in a preclinical study unlocked the promise of CAR T-cell therapy for treatment of solid tumors. The results were published today in the journal Nature.

"Our work extends from the basic biology of T lymphocytes to a possible application in the clinic, with an exploration of deep molecular mechanisms along the way," said co-corresponding author Doug Green, Ph.D., St. Jude Department of Immunology chair. "We found that just like many of us, if you are an activated T cell, things that happen early in your life can impact your later development. We identified that an interaction between the protein c-Myc and the complex cBAF early in T-cell activation influences cell fate trajectory."

Chimeric antigen receptor (CAR) T cells are a type of immunotherapy that modifies a patient's immune cells to target cancer cells. This type of therapy has had remarkable success in treating children and adults with leukemia and lymphoma, particularly in relapsed patients. However, CAR T cells have not had the same success against solid tumors, with problems involving persistence and function.

Currently too many CAR T cells become effector cells, those that directly kill infected or cancerous cells. Too few become memory cells that persist and create more T cells over the long term. The researchers believed that if they created more memory cells, they could improve CAR T-cell therapy.

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An app to help doctors help patients with leukemia
https://medicalxpress.com/news/2022-06- ... kemia.html
by University of Copenhagen

Within five years, 25% of patients suffering from chronic Lymphocytic leukemia (CLL) will develop a serious infection or need early treatment for CL: 10% of these risk dying within a month.

In order to help these patients, doctors would like to be able to identify those at risk of developing infections immediately after they have been diagnosed with CLL.

A team of researchers from the University of Copenhagen and Rigshospitalet has made this their mission, and this has led to the development of an app.

Chief physician and Clinical Associate Professor Carsten Niemann, who is part of the team responsible for the new study, explains:

"It has improved our chances of identifying those patients, once diagnosed, who will require treatment and close follow-up. We have developed an app that allows doctors to enter previous and current blood test results and thus receive data on the individual patient's risk of a severe course of illness," says Carsen Niemann from the Department of Clinical Medicine at the University of Copenhagen and the Department of Haematology at Rigshospitalet, Denmark's leading hospital.

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Combination treatment may improve quality of life in kidney cancer
https://medicalxpress.com/news/2022-06- ... idney.html
by Melissa Rohman, Northwestern University

Patients with advanced kidney cancer who received a new combination treatment reported health-related quality of life outcomes that were either similar or improved, compared to patients who received standard first-line therapy, according to a study published in The Lancet Oncology.

The findings underscore the potential for the new treatment combination in improving patients' course of treatment and extending survival, said David Cella, Ph.D., the Ralph Seal Paffenbarger Professor and chair of the Department of Medical Social Sciences, and senior author of the study.

"Effective treatment options have never been better for this disease and yet more progress is needed. Patients' reports of how they are feeling and functioning is certainly meaningful to them, and also can help clinicians when guiding continued quality care," said Cella, who is also director of the Center for Patient-Centered Outcomes, part of the Institute for Public Health and Medicine (IPHAM), and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Advanced kidney cancer occurs when cancer cells inhibit the inner lining of kidney tubules, which help filter and clean the blood. Over the last 20 years, treatments for the disease have improved, transitioning from biologic response-modifying drugs to more targeted therapies such as tyrosine kinase inhibitors and mTOR inhibitors.

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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."