Tag: melanoma

Categories : CancerTags :

Existing Drug Class May Help Patients with Immunotherapy-resistant Melanoma

On By ModernMedia
3D structure of a melanoma cell derived by ion abrasion scanning electron microscopy. Credit: Sriram Subramaniam/ National Cancer Institute

Increased activity in a specific biological pathway may explain why many patients with a deadly form of skin cancer do not respond to the latest cancer treatments, a new study shows.

Publishing in the journal Cancer Research, the study featured data generated from experiments with human tissues and cells from patients with advanced melanoma that were implanted into mice. Results uncovered therapeutic targets that could limit melanoma growth in patients whose cancer failed to respond to initial treatment with immune checkpoint inhibitors.

Led by researchers at NYU Langone Health and its Perlmutter Cancer Center, the study focused on a subgroup of melanoma patients with mutations in the neurofibromin 1 (NF1) gene. NF1 mutations are just one type among several mutations, including those in the BRAF, NRAS, and PARP genes, that are linked to many cases of cancer, particularly melanoma. As many as 27% of melanoma patients are estimated to have NF1 mutations.

While immunotherapy, which stimulates the immune system to attack cancer cells as it would an invading virus, has proved to be a successful treatment, it does not work well for more than half of NF1-mutant melanoma patients.

“There is a pressing need for new drug therapies for melanoma patients with neurofibromin 1 mutations that do not respond to the latest immunotherapy, and for which there are no subsequent effective treatment options,” said study lead investigator Milad Ibrahim, PhD. Ibrahim is a postdoctoral fellow in the Dr Iman Osman Laboratory in the Ronald O. Perelman Department of Dermatology at the NYU Grossman School of Medicine.

To investigate why these patients were treatment resistant, investigators examined tumour cells from 30 melanoma patients who did not respond to immunotherapy. NF1 mutations were found in 40% of these melanoma samples. The samples came from NYU Langone’s extensive repository from more than 6000 melanoma patients.

Molecular testing showed that the signalling pathway built around a protein called epidermal growth factor receptor (EGFR) was more active in NF1 mutant melanoma cells than in cells with other melanoma-gene mutations. Increased EGFR activity has long been linked to abnormal cell growth in tumours and shorter survival with various cancers. The researchers also found that NF1 mutant melanoma cells depended on increased EGFR activity for survival, regardless of the presence of other mutations.

Because EGFR-inhibiting drugs are already used to treat some head and neck cancers, as well as colorectal and lung cancers, researchers then tested two drugs in the class, cetuximab and afatinib, in both NF1 mutant cell cultures and cancer cell lines without NF1 mutations. After transplanting both tumour cell types into mice and treating them with these drugs, results showed that both EGFR inhibitors were effective against cells and transplanted tumours with NF1 mutations, and they had no effect on melanomas without NF1 mutations.

“Our study results reveal a unique vulnerability in melanoma patients with neurofibromin 1 mutations, that an overexpression of the epidermal growth factor receptor pathway is essential for their survival and growth,” said the study’s senior investigator, Professor Iman Osman, MD.

“While further tests are needed, our results support a novel approach of deploying EGFR inhibitors either alone or in combination with other immunotherapies for treatment of melanoma patients whose tumours harbour NF1 mutation,” said the study’s co-senior investigator, Associate Professor Markus Schober, PhD.

However, Schober says this requires further testing in a clinical trial, which the research team plans to develop. He adds that if trial findings prove successful, the team’s research could provide a lifeline for many of these melanoma patients.

Source: NYU Langone Health

Categories : CancerTags :

Study Identifies Mitochondrial Drivers of Skin Cancer Aggressiveness – and Possible Treatments

On By ModernMedia

Mitochondrial pathways help melanoma cells become aggressive, and some currently available drugs target these pathways.

3D structure of a melanoma cell derived by ion abrasion scanning electron microscopy. Credit: Sriram Subramaniam/ National Cancer Institute

Researchers have discovered that the most aggressive melanomas, the deadliest form of skin cancer, overactivate two key processes in mitochondria. Blocking these pathways with currently available drugs effectively killed melanoma cells. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

By mapping the proteins expressed in 151 tumour and normal skin samples, investigators found that the most aggressive melanomas hyper-activate the machinery that builds mitochondrial proteins and the mitochondrial system that turns nutrients into energy.

Remarkably, blocking these pathways effectively halted or killed melanoma cells cultured in lab dishes. Two types of drugs accomplished this: antibiotics, originally designed to block bacterial protein synthesis machinery, which closely resembles the machinery found in mitochondria, and specialised energy-production inhibitors. Importantly, non-cancerous skin cells remained mostly unaffected, highlighting the safety and specificity of these treatment approaches.

“This discovery identifies melanoma’s excessive reliance on mitochondrial energy as its Achilles’ heel, revealing a therapeutic vulnerability that we can exploit with existing drugs,” said senior author Jeovanis Gil, PhD, of Lund University in Sweden. “By pairing mitochondrial blockers with today’s standards of care, we may cut off a major escape route that cancers use to resist therapy and come back.”

Dr Gil added that the mitochondrial-protein signature his team discovered can be measured in routine biopsy material and could serve as a biomarker to identify patients most likely to benefit from mitochondrial-targeted add-on therapies. By enabling clinicians to match treatments to each patient’s tumour biology, these findings mark a step forward for precision medicine in melanoma. Moreover, because mitochondrial rewiring fuels resistance across many cancers, success in melanoma could open the door to similar personalised combination strategies in other hard-to-treat cancers. 

Source: Wiley

Categories : CancerTags :

How to Stop Melanoma’s Incredibly Swift Evasion of Treatment

On By ModernMedia
Melanoma Cells. Credit: National Cancer Institute

Researchers have uncovered a stealth survival strategy that melanoma cells use to evade targeted therapy, offering a promising new approach to improving treatment outcomes.

The study, published in Cell Systems and conducted by researchers at the Institute for Systems Biology (ISB) and Massachusetts Institute of Technology (MIT) identifies a non-genetic, reversible adaptation mechanism that allows melanoma cells to survive treatment with BRAF inhibitors. By identifying and blocking this early response, researchers proposed a combination therapy that could delay resistance and enhance the effectiveness of existing treatments.

Cracking the Code of Melanoma’s Drug Escape

Melanoma, the deadliest form of skin cancer, is often driven by mutations in the BRAF gene, which fuels uncontrolled tumor growth. While BRAF inhibitors (such as vemurafenib) initially halt tumor growth, many tumors quickly adapt and survive treatment, leading to therapy failure.

Unlike traditional resistance driven by genetic mutations, this study uncovers an early, dynamic adaptation process that occurs within hours to days of drug treatment – long before genetic resistance takes hold. Surprisingly, this process does not rely on reactivating the BRAF-ERK pathway, which is the usual resistance mechanism.

Using cutting-edge mass spectrometry-based phosphoproteomics and deep transcriptomics analyses, researchers mapped the molecular shifts in melanoma cells over minutes, hours, and days of BRAF inhibitor treatment.

“We found that while the BRAF-ERK signaling pathway was quickly and durably suppressed, cancer cells did not rely on reactivating ERK to survive. Instead, they triggered an alternative SRC family kinase (SFK) signaling pathway, which promoted cell survival and eventual recovery,” said Chunmei Liu, PhD, a bioinformatics scientist at ISB and co-first author of the paper.

Turning a Weakness Into a Target

A key discovery in this study came when researchers linked SFK activation to reactive oxygen species (ROS), a cellular stress response that builds up under BRAF inhibition. As ROS levels surged, SFK activity spiked, helping melanoma cells withstand treatment. However, this adaptation was reversible – when treatment was removed, cells returned to their original state.

Recognizing this Achilles’ heel, the team tested a combination approach: pairing BRAF inhibitors with the SFK inhibitor dasatinib.

“By adding dasatinib, we blocked this adaptive escape mechanism, significantly reducing melanoma cell survival and stabilising tumours in animal models,” said ISB Associate Professor Wei Wei, PhD, co-corresponding author.

Importantly, SFK inhibition alone had little effect on melanoma cells, highlighting the need for a strategic combination therapy to suppress melanoma adaptation before resistance fully develops. 

“This approach has the potential to prolong the effectiveness of BRAF inhibitors and improve patient outcomes,” said ISB President and Professor Jim Heath, PhD, co-corresponding author.

Looking Ahead: A Path to the Clinic

Beyond uncovering a key mechanism of drug adaptation, this research underscores the importance of early intervention to prevent it from happening. It also highlights ROS accumulation and SFK activation as potential biomarkers for identifying patients who may benefit from this combination therapy.

Further preclinical studies and clinical trials will be necessary to validate this combination therapy strategy and determine its potential for broader clinical use.

Source: Institute for Systems Biology

Categories : CancerTags :

New Combination Immunotherapy for Melanoma and Breast Cancer

On By ModernMedia
3D structure of a melanoma cell derived by ion abrasion scanning electron microscopy. Credit: Sriram Subramaniam/ National Cancer Institute

A research team at the Medical University of Vienna led by Maria Sibilia has investigated a new combination therapy against cancer. This therapy employs systemic administration of the tissue hormone interferon-I combined with local application of Imiquimod. Promising results were seen in topically accessible tumours like melanoma and breast cancer models: the therapy led to the death of tumour cells at the treated sites and simultaneously activated the adaptive immune system to fight even distant metastases. The findings, published in Nature Cancer, could improve the treatment of superficial tumours such as melanoma and breast cancer.

In recent years, immunotherapies have had significant success in the treatment and cure of a wide range of cancers. However, for some patients, these agents are still not sufficiently effective. As part of a preclinical study, Maria Sibilia, Head of the Center for Cancer Research at the Medical University of Vienna, therefore investigated the effects of a combination immunotherapy consisting of systemic administration of the tissue hormone interferon (IFN)-I and local imiquimod therapy. Imiquimod is an active substance that activates the innate receptors TLR7/8 and used to treat basal cell carcinomas. The researchers employed various preclinical mouse tumour models of melanoma and breast cancer. What both tumours have in common is that they are accessible to local therapy and often form distant metastases.

Effective for local tumours and distant metastases

Immunotherapies use the body’s own immune system to fight cancer cells. Plasmacytoid dendritic cells (pDCs), which are activated by Imiquimod via TLR7/8, play an important role in this process. The study showed that oral imiquimod stimulates pDCs to produce the tissue hormone IFN-I. This sensitised other dendritic cells and macrophages in the tumour environment to topical imiquimod therapy, which inhibited the formation of new blood vessels via the cytokine IL12 leading to the death of tumour cells.
The combination immunotherapy not only had an effect on the treated tumours, but also on distant metastases. It reduced the formation of new metastases thus preventing tumour relapses and increasing the sensitivity of melanomas to checkpoint inhibitors.

“These findings illustrate that the combination of systemic treatment with imiquimod or IFN-I and topical therapy with imiquimod has the potential to expand treatment options for patients and improve therapy outcomes in locally accessible tumors such as melanoma or breast cancer,” emphasizes Maria Sibilia.
“Topical treatment of the primary tumor with imiquimod is essential for this combination therapy with systemic IFN-I to be effective at the treated site and also to clear distant metastases,” adds Philipp Novoszel, MedUni Vienna, one of the first authors of the study.

The results suggest that this therapeutic strategy has the potential to improve treatment outcomes in superficial and thus locally accessible tumors such as melanoma and breast cancer – on the one hand through therapy-associated cancer cell death at the locally treated tumors, but also through the induction of a T cell-induced anti-tumor immune response at distant metastases, which is further enhanced by checkpoint inhibitors.

“Our aim is to continue developing immunotherapeutic strategies in order to improve the long-term prospects for patients who are not yet responding well to these agents,” says Maria Sibilia, who is also Deputy Head of the Comprehensive Cancer Center of MedUni Vienna and University Hospital Vienna.
“As systemic interferon is a well-known cancer therapy and dendritic cells are activated in a similar way to our preclinical models, we believe that the new combination therapy can show an effect in patients,” adds Martina Sanlorenzo, dermato-oncologist at MedUni Vienna and co-first author of the study.

Publication: Nature Cancer
Systemic IFN-I combined with topical TLR7/8 agonists promotes distant tumor-suppression by c-Jun-dependent IL-12 expression in dendritic cells
Sanlorenzo M, Novoszel P, Vujic I, Gastaldi T, Hammer M, Fari O, De Sa Fernandes C, Landau AD, Göcen-Oguz BV, Holcmann M, Monshi B, Rappersberger K, Agnes Csiszar A, Sibilia M
DOI: 10.1038/s43018-024-00889-9; https://www.nature.com/articles/s43018-024-00889-9

Source: Medical University of Vienna

Categories : CancerTags :

How, When and Where: Sex Matters in Melanoma Development

On By ModernMedia
Photo by Rfstudio on Pexels

Melanoma rates differ consistently between men and women in terms of the ages at which melanomas occur and the locations on the body where they occur. Over time, melanoma rates have increased in both men and women, but the trends differ by body site. A new study in the Journal of Investigative Dermatology, published by Elsevier, presents the findings from a large-scale, long-term melanoma data analysis investigating incidence trends by age, sex, and anatomic site.

Lead investigator David C. Whiteman, MBBS, PhD, Cancer Control Group, QIMR Berghofer Medical Research Institute, and Faculty of Medicine, The University of Queensland, Brisbane, Australia, explains, “There has been a general observation in numerous populations that melanomas appear to arise at different rates in men and women. We decided to investigate this observation rigorously and assess whether these differences have been constant through time or across generations by using large-scale data from population registries to investigate long-term melanoma trends in men and women.”

The research team analysed more than 40 years of melanoma data from Queensland, Australia, the USA, and Scotland. These three populations were chosen because historically they have had high (Queensland), moderate (USA), and low (Scotland) rates of melanoma. Over time, the rates of melanoma increased in all three populations, especially among women. In women in all populations, melanomas arise most commonly on the limbs, whereas in men, melanomas arise most commonly on the trunk and head and neck. In both sexes, there has been a steady increase in melanomas on the head and neck with increasing age.

Researchers found that in virtually all investigated populations, women experience higher rates of melanoma than men in early life (up to age ~45 years), but men develop melanomas at higher rates than women later in life (from ages ≥ 65 years). Furthermore, these sex-specific trends reflect complex patterns of incidence across body sites that vary consistently with age. Thus, in early life, women experience higher rates of lower limb melanomas than men, which persists into older ages. Also, on the upper limbs, women experience substantially higher rates than men from young ages until middle age (45–64 years), after which men experience higher rates. In contrast, on the head and neck and the trunk, melanomas occur at higher incidence in men than in women early in life. On all body sites, the rate at which melanoma incidence rises with age is much more rapid for men than for women.

The study confirms that men and women experience melanoma in different ways. While this is most likely driven by different patterns of sun exposure between men and women, there appear to be inherent differences in the ways in which melanomas develop at different body sites in women compared with men. Understanding the underlying biological differences could provide important clues about the etiology of this enigmatic cancer.

Source: Elsevier

Categories : Cardiovascular Disease Environmental EffectsTags :

Benefits of UV Exposure may Outweigh Risks in Low-sunlight Countries

On By ModernMedia
Photo by Julian Jagtenberg on Pexels

The health benefits of spending time in the sun could outweigh the risks for those living in areas with limited sunshine, a UK study suggests. In low-sunlight locations such as parts of the UK, exposure to higher levels of ultraviolet (UV) radiation was linked to a drop in deaths due to cardiovascular disease and cancer.

Adapting public health advice to reflect both the risks and benefits of UV exposure may help to reduce disease burden and improve life expectancy in low-sunlight countries, the research team says.

Experts caution that measures should still be taken to protect the skin when UV levels are high, to prevent sunburn and the development of skin cancer.

Volunteer data

University of Edinburgh scientists used genetic and health information from the UK BioBank – an anonymised database of health details from volunteers – to examine the UV exposure of 395 000 people across the UK. Participants were restricted to those of white European descent, due to the role skin pigmentation plays in the body’s response to UV exposure.

The team applied two measures to identify those exposed to higher levels of UV. They used the geographical location of participants to calculate their average annual exposure to solar energy and, separately, whether they used sunbeds.

The findings were adjusted for other factors that might influence health – including smoking, exercise, social deprivation and gender – to reduce the chance that these factors were responsible for any of the changes observed.

Health impact

Living in locations with higher UV levels, for example Cornwall, was associated with a lower risk of death from cardiovascular disease and cancer – 19% and 12%, respectively – than living in areas with lower UV levels, such as Edinburgh or Glasgow.

Sunbed use was linked to a 23% lower risk of death from cardiovascular disease and a 14% lower risk of death from cancer, compared to non-users. It is possible that people who use sunbeds may also seek out greater sun exposure and so this result may reflect broader sun seeking behaviour, the team says.

Those with a higher estimated UV exposure had a slightly increased risk of being diagnosed with melanoma, but their risk of dying from the condition was not raised.

As the study is based on UK data from a white European population, the findings are of most relevance to similar groups in low-sunlight countries. Further research into locations with higher UV exposure is needed to build a clearer picture of the potential benefits to health, experts say.

The study, funded by Health Data Research UK, is published in the journal Health and Place.

Our paper adds to a growing body of evidence suggesting that in lower light environments, relatively higher exposure to UV is good for your health. Though there may be an increased risk of skin cancer incidence with higher UV exposure, this risk appears to be outweighed by a larger reduction in the risk of death from cancer and cardiovascular related disease.

Professor Chris Dibben, University of Edinburgh’s School of GeoSciences

Dermatologists have traditionally only considered possible harm to the skin caused by sunlight, much of which dates from the experience of white-skinned individuals in sunny countries such as Australia. When the UV index is very high, protecting skin is important.

However, this research shows that in the UK, the balance of benefit and risk from sunlight exposure is probably very different from that in sunnier countries.

Professor Richard Weller, University of Edinburgh’s Centre for Inflammation Research

Source: The University of Edinburgh

Categories : CancerTags :

Unique Genetic Pattern can Predict Severe Side Effects of Melanoma Immunotherapy

On By ModernMedia
Melanoma Cells. Credit: National Cancer Institute

An activity pattern in certain genes responsible for building proteins known as spleen tyrosine kinases can predict which melanoma patients are likely to have severe side effects from immunotherapy designed to treat the most deadly skin cancer, as shown by a new study published in the journal Clinical Cancer Research.

Led by researchers at NYU Langone Health and its Perlmutter Cancer Center, the latest experiments focused on checkpoint inhibitors, drugs that have in the last decade become a mainstay of treating melanoma. This form of skin cancer kills nearly 10 000 Americans annually.

The drugs work by blocking molecules (checkpoints) that sit on the surface of immune T which the immune system uses to recognise and protect healthy cells. Cancer cells are able to hijack and turn off immune cell surveillance, evading detection. Immunotherapy drugs like nivolumab and ipilimumab are designed to block checkpoints, making cancer cells more “visible” again to T cells.

More than a third of melanoma patients given checkpoint inhibitors develop side effects so severe that they compromise their quality of life and ability to continue therapy. Side effects most often involve some form of inflammation, a sign of an overactive immune response. Patients may experience severe skin rashes, diarrhoea, or hyperthyroidism. More-severe side effects can include liver toxicity, colitis, and rheumatoid arthritis.

In the new study researchers found that even before treatment began in their test subjects, the activity of genes controlling the production of spleen tyrosine kinases predicted 83% of melanoma patients who eventually developed severe side effects from combined immunotherapy with nivolumab and ipilimumab.

Moreover, the researchers found that this heightened gene signature, as evidenced by the production of spleen tyrosine kinases, or the SYK pathway, did not interfere with the effectiveness of therapies in preventing recurrence of melanoma. The impact was connected only to side effects.

“Predictive information of this kind is critically important to oncologists and patients to help guide their immunotherapy decisions, to either minimize these side effects by taking additional precautions or to choose alternative immunotherapies,” said study co-senior investigator Tomas Kirchhoff, PhD.

“Our study results show that increased gene activity in the spleen tyrosine kinase pathway could be the basis of a possible blood test that identifies those melanoma patients most susceptible to having severe side effects from immunotherapy, and well before they start treatment,” said study co-lead investigator Kelsey Monson, PhD. 

For the study, researchers analysed immune system cell samples from 212 men and women with melanoma participating in the CheckMate-915 trial. The trial was designed to test whether combined therapy with nivolumab and ipilimumab worked better than single therapy with nivolumab in preventing postsurgical recurrence of melanoma. All immune cell samples were taken prior to the start of immunotherapy. Both drugs are manufactured by the pharmaceutical company Bristol Myers Squibb, which sponsored the CheckMate-915 trial, and provided the patient specimens and data used in the analysis.

When researchers looked at what genes were more active than others in patients who experienced side effects from their immunotherapy, they found a specific pattern among 24 genes tied to the production of spleen tyrosine kinases. Further statistical analyses showed that increased or decreased activity (transcription) of only five of these genes – CD22, PAG1, CD33, HNRNPU, and FCGR2C – along with patients’ age and the stage severity of their melanoma served as the best predictors of who would experience side effects from immunotherapy.

Study co-senior investigator Jeffrey S. Weber, MD, PhD, says that the SYK pathway has previously been linked to other autoimmune diseases, including lupus, rheumatoid arthritis, and colitis. He also points out that immunotherapy side effects were also most common in areas affected by these autoimmune diseases, including the skin, colon, and liver.

Dr Weber says the team next plans to investigate if an activated SYK pathway is predictive of side effects in patients treated with ipilimumab alone or with other combination immunotherapies.

“If our future research can explain how an activated spleen tyrosine kinase pathway leads to increased risk of side effects from immunotherapy, then it could also potentially help us to design better cancer immunotherapies and potentially other treatments for autoimmune diseases,” said Dr Kirchhoff.

Source: NYU Langone Health / NYU Grossman School of Medicine

Categories : CancerTags :

Malignant Melanoma Resists Treatment by Subverting Immune Cells

On By ModernMedia
3D structure of a melanoma cell derived by ion abrasion scanning electron microscopy. Credit: Sriram Subramaniam/ National Cancer Institute

Malignant melanoma is one of the most aggressive types of cancer. Despite recent progress in effective therapies, the tumours of many patients are either resistant from the outset or become so during the course of treatment.

A University of Zurich (UZH) study published in Cell Reports Medicine has now identified a mechanism involving subverted immune cells that impedes the effectiveness of therapies. The result provides new ideas for treatments to suppress the development of resistance.

Comparing resistant and non-resistant tumour cells

For the study, the team utilised an innovative fine-needle biopsy to sample tumour cells before and during therapy. This allowed the researchers to analyse each cell individually. The patients providing the samples were undergoing targeted cancer therapy for malignant melanoma, which inhibits signalling pathways for tumour formation.

“It was important that some of the tumours responded to the therapy, while others showed resistance,” says study leader Lukas Sommer, professor of stem cell biology at the Institute of Anatomy at UZH. This allowed the team to compare the metabolism and environment of resistant and non-resistant tumour cells and look for significant differences.

Interaction between tumour factor and immune cells

One of the most relevant findings concerned the POSTN gene: it codes for a secreted factor that plays an important role in resistant tumours. In fact, the tumours of patients with rapidly progressing disease despite treatment showed increased POSTN levels. In addition, the microenvironment of these tumours contained a larger number of a certain type of macrophage – a subtype of immune cell that promotes the development of cancer.

Through a series of further experiments – both with human cancer cells and with mice – the research team was able to show how the interaction of increased POSTN levels and this type of macrophage triggers resistance: the POSTN factor binds to receptors on the surface of the macrophages and polarises them to protect melanoma cells from cell death. “This is why the targeted therapy no longer works,” says Sommer.

No resistance without cancer-promoting macrophages

The team considers this mechanism a promising starting point. “The study highlights the potential of targeting specific types of macrophages within the tumour microenvironment to overcome resistance,” says Sommer. “In combination with already known therapies, this could significantly improve the success of treatment for patients with malignant melanoma.”

Source: University of Zurich

Categories : Cancer DermatologyTags :

Among Black Men, Study Finds Increased Mortality from Melanoma Diagnoses

On By ModernMedia
Photo by Nsey Benajah on Unsplash

Melanoma is often detected later in people with darker skin complexions – and the consequences can be devastating, according to the results of a Mayo Clinic study published in the Journal of Surgical Oncology.

While melanoma may be found less frequently in people with darker complexions than fair ones, this aggressive form of skin cancer, accounting for 75% of all skin-cancer-related deaths, can strike anyone. The study, which consisted of 492 597 patients with melanoma, suggests that added vigilance in early screening is particularly needed for Black men, whose cancers are often found at later stages, leading to worse outcomes compared to white patients or Black women.

“We compared non-Hispanic Black patients to white patients and saw striking differences in how patients presented with the disease,” says surgical oncologist Tina Hieken, MD, senior author of the study and a researcher at Mayo Clinic Comprehensive Cancer Center. “We saw more extremity melanoma, and more later-stage disease.”

Extremity melanoma refers to skin cancer that can develop on the arms, legs, hands and feet. Various factors, including social risk factors and biological components, could be at play, but further research is needed to help determine why these differences exist.

Revealing differences in sex-based immune response

The research found that Black female patients with melanoma fared better than Black male patients. Men tended to be older at diagnosis and more likely to have cancer that had spread to their lymph nodes compared to women. This translated to worse survival rates: the five-year survival for Black men with stage 3 melanoma was only 42% chance, compared to 71% for Black women.

Most research on melanoma hasn’t focused on how race and sex affect outcomes and hasn’t looked at the influence of race and ethnicity across all groups. Dr Hieken says the study highlights the need to understand these differences better, noting that this is the first large study to confirm that sex-based differences in melanoma outcomes exist within the non-Hispanic Black population.

“When we talk about later-stage melanoma patients who are female versus male in that non-Hispanic Black patient cohort who ended up doing worse, some biological things may be going on here that are interesting,” says Dr Hieken.

One theory centres on variations in immune response.

“Several immune signals suggest that women may respond better to some immunotherapies than males,” says Dr Hieken.

Researchers note that more studies focused on melanoma in a broader range of people, including more Black participants in clinical trials, is key to bridging this knowledge gap and potentially identifying more effective treatments.

Healthcare professionals should screen carefully

Dr Hieken notes that this study is a wake-up call for everyone battling to diagnose and cure melanoma, regardless of the patient’s sex or skin tone.

She emphasises that healthcare professionals should carefully examine areas like palms, soles and under fingernails, where melanoma might be more challenging to spot on darker skin.

“We can incorporate screening for skin lesions or lesions under the nails into the visit for patients as part of their regular checkups,” says Dr Hieken. “What we want to do is elevate care for our patients.”

Source: Mayo Clinic

Categories : Cancer IT in HealthcareTags :

AI-based App can Help Physicians Diagnose Melanomas

On By ModernMedia
3D structure of a melanoma cell derived by ion abrasion scanning electron microscopy. Credit: Sriram Subramaniam/ National Cancer Institute

A mobile app that uses artificial intelligence, AI, to analyse images of suspected skin lesions can diagnose melanoma with very high precision. This is shown in a study led from Linköping University in Sweden where the app has been tested in primary care. The results have been published in the British Journal of Dermatology.

“Our study is the first in the world to test an AI-based mobile app for melanoma in primary care in this way. A great many studies have been done on previously collected images of skin lesions and those studies relatively agree that AI is good at distinguishing dangerous from harmless ones. We were quite surprised by the fact that no one had done a study on primary care patients,” says Magnus Falk, senior associate professor at the Department of Health, Medicine and Caring Sciences at Linköping University, specialist in general practice at Region Östergötland, who led the current study.

Melanoma can be difficult to differentiate from other skin changes, even for experienced physicians. However, it is important to detect melanoma as early as possible, as it is a serious type of skin cancer.

There is currently no established AI-based support for assessing skin lesions in Swedish healthcare.

“Primary care physicians encounter many skin lesions every day and with limited resources need to make decisions about treatment in cases of suspected skin melanoma. This often results in an abundance of referrals to specialists or the removal of skin lesions, which in the majority of cases turn out to be harmless. We wanted to see if the AI support tool in the app could perform better than primary care physicians when it comes to identifying pigmented skin lesions as dangerous or not, in comparison with the final diagnosis,” says Panos Papachristou, researcher affiliated with Karolinska Institutet and specialist in general practice, main author of the study and co-founder of the company that developed the app.

And the results are promising.

“First of all, the app missed no melanoma. This disease is so dangerous that it’s essential not to miss it. But it’s almost equally important that the AI decision support tool could acquit many suspected skin lesions and determine that they were harmless,” says Magnus Falk.

In the study, primary care physicians followed the usual procedure for diagnosing suspected skin tumours. If the physicians suspected melanoma, they either referred the patient to a dermatologist for diagnosis, or the skin lesion was cut away for tissue analysis and diagnosis.

Only after the physician decided how to handle the suspected melanoma did they use the AI-based app. This involves the physician taking a picture of the skin lesion with a mobile phone equipped with an enlargement lens called a dermatoscope. The app analyses the image and provides guidance on whether or not the skin lesion appears to be melanoma.

To find out how well the AI-based app worked as a decision support tool, the researchers compared the app’s response to the diagnoses made by the regular diagnostic procedure.

Of the more than 250 skin lesions examined, physicians found 11 melanomas and 10 precursors of cancer, known as in situ melanoma. The app found all the melanomas, and missed only one precursor. In cases where the app responded that a suspected lesion was not a melanoma, including in situ melanoma, there was a 99.5% probability that this was correct.

“It seems that this method could be useful. But in this study, physicians weren’t allowed to let their decision be influenced by the app’s response, so we don’t know what happens in practice if you use an AI-based decision support tool. So even if this is a very positive result, there is uncertainty and we need to continue to evaluate the usefulness of this tool with scientific studies,” says Magnus Falk.

The researchers now plan to proceed with a large follow-up primary care study in several countries, where use of the app as an active decision support tool will be compared to not using it at all.

Source: Linköping University