Category: Cancer

Categories : Cancer Obstetrics & GynaecologyTags :

Groundbreaking Ovarian Cancer Research Targets Cells that Fuel Tumour Growth

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Female reproductive system. Credit: Scientific Animations CC4.0 BY-SA

In a recent paper published in Nature, researchers at the University of Chicago discovered how to block nicotinamide N-methyl transferase (NNMT), an enzyme that is involved in the progression of high-grade serous ovarian cancer. The team showed that NNMT promotes cancer growth by helping the tumour evade the immune system, and they also developed a potent NNMT inhibitor that could help overcome therapy resistance, providing a new and effective strategy for treating ovarian cancer.

A common yet deadly form of ovarian cancer

High-grade serous ovarian cancer is the most common and deadly form of ovarian cancer. It is often diagnosed at advanced stages and is notoriously challenging to treat. Although surgery and chemotherapy initially provide substantial benefits, the cancer frequently recurs, leading to low survival rates. Immunotherapy, a breakthrough treatment for many cancers, has failed in ovarian cancer, largely because activity of surrounding cells has been programmed by the tumour to suppress the immune response. These cells, known as cancer-associated fibroblasts (CAFs), differ from normal fibroblasts, which play a vital role in supporting tissue integrity and facilitating wound healing. Instead, CAFs surround the tumor, offer protection, and release signals that weaken immune responses and promote metastasis.

“Most therapies focus on the cancer cells, but we are interested in the fibroblasts in the surrounding stroma. These cells don’t mutate like cancer cells, which makes them more stable and, we think, more targetable,” said Ernst Lengyel, MD, PhD, Professor and Chair of Obstetrics and Gynecology at UChicago and lead author of the paper. “We have pinpointed the mechanism behind CAF activation and found a drug that can halt it in its tracks.”

NNMT: A master regulator

In a landmark 2019 Nature study, Lengyel’s team showed that NNMT, a metabolic enzyme, is highly expressed in CAFs and converts normal fibroblasts into tumour-promoting fibroblasts by changing epigenetic and metabolic programming. The new Nature study demonstrates how NNMT promotes immune evasion and how to stop it. The UChicago team discovered that NNMT-expressing CAFs secrete complementary proteins, which convert monocytes (a type of white blood cells) into myeloid-derived suppressor cells (MDSCs).

“The enzyme NNMT induces widespread epigenetic changes in fibroblasts that promote tumour growth. Inhibiting NNMT has the potential to reverse these changes and reduce the tumour-supportive role of fibroblasts,” says Janna Heide, MD, a postdoctoral researcher in the Lengyel Lab and first author of the study.

Better results with combined NNMT inhibitor and immunotherapy

To translate these findings into treatment, the team collaborated with scientists at the National Center for Advancing Translational Sciences (NCATS) and the National Cancer Institute (NCI) Experimental Therapeutics (NExT) program, which supports early-stage drug development with high translational potential. After screening over 150 000 compounds, they identified a highly targeted NNMT inhibitor. In preclinical animal models of ovarian cancer, the NNMT inhibitor decreased tumour burden and restored immune activity. Most importantly, when the inhibitor was combined with immune checkpoint inhibitors, it halted tumour growth.

Historically, drug development has focused almost entirely on cancer cells. This study demonstrates that non-cancerous cells in the tumour microenvironment can also play a crucial role in disease progression and treatment resistance. Targeting CAFs through NNMT inhibition offers a new therapeutic approach to overcome these barriers.

“Immunotherapy hasn’t worked in ovarian cancer, but the combination therapy of an NNMT inhibitor with immunotherapy worked remarkably well in our preclinical models,” Lengyel said. “It was exciting to show that tumor growth can be controlled without even touching the cancer cells, just by reprogramming the supporting cells around them.”

Lengyel said this research was only possible through the partnership with the National Center for Advancing Translational Sciences and the collaborative spirit at the UChicago, particularly with Ralph Weichselbaum, MD, Chair of the Department of Radiation Oncology, an expert in immune regulation, and his team, including postdoctoral researcher András Piffkó, MD. This work is part of Lengyel’s broader efforts to transform ovarian cancer treatment, supported by an NCI Outstanding Investigator Award (R35), which funds long-term, high-impact research with the potential to change clinical practices.

“Without NIH funding, we simply couldn’t have accomplished this,” Lengyel said. “It allowed us to take risks, innovate, and ultimately develop something that might help patients.”

Source: University of Chicago Medicine

Categories : Cancer Diet and NutritionTags :

Animal Protein Not Linked to Higher Mortality Risk, Study Finds

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Photo by Jose Ignacio Pompe on Unsplash

Eating animal-sourced protein foods is not linked to a higher risk of death and may even offer protective benefits against cancer-related mortality, new research finds.   

The study, published in Applied Physiology, Nutrition, and Metabolism, analysed data from nearly 16 000 adults aged 19 and older using the National Health and Nutrition Examination Survey (NHAMES III). 

Researchers examined how much animal and plant protein people typically consume and whether those patterns were associated with their risk of dying from heart disease, cancer or any cause.  

They found no increased risk of death associated with higher intake of animal protein. In fact, the data showed a modest but significant reduction in cancer-related mortality among those who ate more animal protein.  

“There’s a lot of confusion around protein – how much to eat, what kind and what it means for long-term health. This study adds clarity, which is important for anyone trying to make informed, evidence-based decisions about what they eat,” explains Stuart Phillips, Professor and Chair of the Department of Kinesiology at McMaster University, who supervised the research.  

To ensure reliable results, the team employed advanced statistical methods, including the National Cancer Institute (NCI) method and multivariate Markov Chain Monte Carlo (MCMC) modelling, to estimate long-term dietary intake and minimize measurement error.   

“It was imperative that our analysis used the most rigorous, gold standard methods to assess usual intake and mortality risk. These methods allowed us to account for fluctuations in daily protein intake and provide a more accurate picture of long-term eating habits,” says Phillips.   

The researchers found no associations between total protein, animal protein or plant protein and risk of death from any cause, cardiovascular disease, or cancer. When both plant and animal protein were included in the analysis, the results remained consistent, suggesting that plant protein has a minimal impact on cancer mortality, while animal protein may offer a small protective effect. 

Observational studies like this one cannot prove cause and effect; however, they are valuable for identifying patterns and associations in large populations. Combined with decades of clinical trial evidence, the findings support the inclusion of animal proteins as part of a healthy dietary pattern.  

“When both observational data like this and clinical research are considered, it’s clear both animal and plant protein foods promote health and longevity,” says lead researcher Yanni Papanikolaou, MPH, president, Nutritional Strategies. 

This research was funded by the National Cattlemen’s Beef Association (NCBA), a contractor to the Beef Checkoff. NCBA was not involved in the study design, data collection and analysis or publication of the findings.  

This article was first published on Brighter World. Read the original article.

Categories : Cancer NeurologyTags :

Researchers Find TBI Link to Development of Malignant Brain Tumours

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Coup and contrecoup brain injury. Credit: Scientific Animations CC4.0

New research led by investigators at Mass General Brigham suggests a link between a history of traumatic brain injury (TBI) and risk of developing a malignant brain tumour. By evaluating data from 2000–2024 of more than 75 000 people with a history of mild, moderate or severe TBI, the team found the risk of developing a malignant brain tumour was significantly higher compared to people without a history of TBI. The results were published in JAMA Network Open.

“I see these results as alarming,” said co-senior author and corresponding author Saef Izzy, MD, FNCS, FAAN, a neurologist and head of the Immunology of CNS Injury Program at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. “Our work over the past five years has shown that TBI is a chronic condition with lasting effects. Now, evidence of a potential increased risk of malignant brain tumours adds urgency to shift the focus from short-term recovery to lifelong vigilance.

“Alongside our earlier findings linking TBI and cardiovascular disease, this underscores the importance of long-term monitoring for anyone with a history of TBI.”

The team divided the severity of TBI between mild, moderate and severe, with participants suffering from incidents ranging from car accidents to falls. In the two categories of moderate and severe, 0.6% of people (87 out of 14 944) developed brain tumours within 3-to-5 years after the TBI, which was a higher percentage than controls. Mild cases of TBI, such as those caused by concussions, were not associated with an increased risk of tumour. The aim of the study was not to establish a cause-and-effect link between moderate-to-severe TBI and malignant tumours, but rather to explore whether an association exists. Determining causality and understanding the underlying mechanisms will require a dedicated translational study in the future.

A previous study showed veterans of the Iraq and Afghanistan wars who suffered TBI experienced an increased risk of brain tumours, but previous studies on civilian populations showed conflicting results. The collaborative team of researchers used an international disease classifying system known as ICD codes to exclude anyone in the study with a history of brain tumour, benign tumours, and risk factors such as radiation exposure.

Previous neurotrauma studies from Mass General Brigham have looked at patients with a history of TBI and found an association with the emergence of anxiety, depression, and other psychiatric, neurological, and cardiovascular diseases, but the current study focuses on malignant tumour development.

Future imaging studies could draw a connection between the location of the TBI and where tumours developed in the brains of participants. The team would like to further study patients with repeated injuries, such as falls. 

“While there is an increased risk of tumour from TBI, the overall risk remains low. Still, brain tumour is a devastating disease and often gets detected in later stages,” said lead author Sandro Marini, MD, a neurologist at Mass General Brigham. “Now, we’ve opened the door to monitor TBI patients more closely.”

Source: Mass General Brigham

Categories : Cancer Medical Research & TechnologyTags :

Cold Plasma Penetrates Deep into Tissue to Attack Tumours

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Researchers at the Leibniz Institute for Plasma Science and Technology (INP) have collaborated with partners at Greifswald University Hospital and University Medical Centre Rostock to demonstrate that cold plasma can effectively combat tumour cells even in deeper tissue layers. What is particularly noteworthy is that, by developing new tissue models, they were able to precisely investigate the effect of individual plasma components on tumour cells for the first time.

The results of the study were published in the journal Trends in Biotechnology.

What is cold plasma?

Plasma is an ionised gas that produces a large number of chemically reactive molecules known as reactive oxygen and nitrogen species. These short-lived molecules can have a strong influence on biological processes such as the growth or death of tumour cells.

New tissue models provide important insights

“The effect of plasma in tissue is very complex and little understood. We have therefore developed a 3D model made of hydrogels that mimics real tumour tissue. In this model, we were able to observe exactly how deep the molecules from the plasma penetrate – and which of these molecules are important for the effect on tumour cells,” explains Lea Miebach, first author of the study. Particularly short-lived molecules such as peroxynitrite penetrated several millimetres deep into the tissue. Hydrogen peroxide, which had previously been considered the main active ingredient in laboratory research, showed little effect: even when it was specifically removed, the effect of the plasma remained strong.

Use during surgery also conceivable

Another model investigated how well plasma could work in the follow-up treatment of tumour surgery. Residual tumour cells at the edge of an artificial surgical wound were specifically treated with plasma. The result: here too, a strong effect was observed, especially in cells that had already spread into the surrounding tissue. These findings could help to better prevent relapses after surgery.

Important step for plasma medicine

“Our results could significantly improve the medical application of plasma,” says Prof Dr Sander Bekeschus, head of the Plasma Medicine research programme at INP. “The better we understand which molecules are active in the tissue, the more precisely plasma devices can be used for specific types of cancer.”

The work was carried out using the medically approved plasma jet “kINPen”. In the long term, the method could help make therapies more effective and gentler.

Source: Leibniz-Institut für Plasmaforschung und Technologie e.V.

Categories : CancerTags :

Existing Drug Class May Help Patients with Immunotherapy-resistant Melanoma

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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 :

Ischaemia Speeds Tumour Growth by Aging the Immune System

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Immune cells (red) accumulating within a tumour (blue) and multiplying (green). When blood flow is blocked either in the heart or legs, these immune cells change in a way that enables tumour growth. Credit: NYU Langone

Cutting off blood flow can prematurely age the bone marrow, weakening the immune system’s ability to fight cancer, according to a new study from NYU Langone Health.

Published online August 19 in JACC: CardioOncology, the study showed that peripheral ischaemia, restricted blood flow in the arteries in the legs, caused breast tumours in mice to grow at double the rate seen in mice without restricted flow. These findings build on a 2020 study from the same team that found ischemia during a heart attack to have the same effect.

Ischaemia occurs when fatty deposits, such as cholesterol, accumulate in artery walls, leading to inflammation and clotting that restrict the flow of oxygen-rich blood. When this happens in the legs, it causes peripheral artery disease, which can increase the risk of heart attack or stroke.

“Our study shows that impaired blood flow drives cancer growth regardless of where it happens in the body,” says corresponding author Kathryn J. Moore, PhD, tProfessor of Cardiology at NYU Grossman School of Medicine. “This link between peripheral artery disease and breast cancer growth underscores the critical importance of addressing metabolic and vascular risk factors as part of a comprehensive cancer treatment strategy.”

Importantly, the research team found that restricted blood flow triggers a shift toward immune cell populations that cannot efficiently fight infections and cancer, mirroring changes seen with aging.

Systemic Skewing

To examine the mechanisms behind the link between cardiovascular disease and cancer growth, the study authors developed a mouse model with breast tumours and induced temporary ischaemia in one hind limb. The team then compared cancer growth in mice with and without impaired blood flow.

Their findings build on the nature of the immune system, which evolved to attack invading bacteria and viruses, and under normal conditions detects and eliminates cancer cells. These protective functions rely on stem cell reserves in the bone marrow, which can be activated as needed to produce key white blood cell populations throughout life.

Normally, the immune system responds to injury or infection by ramping up inflammation to eliminate threats, then scaling back to avoid harm to healthy tissue. This balance is maintained by a mix of immune cells that either activate or suppress inflammation. The researchers found that reduced blood flow disrupts this equilibrium. It reprograms stem cells in the bone marrow to favour the production of “myeloid” immune cells (monocytes, macrophages, neutrophils) that dampen immune responses, while reducing output of lymphocytes like T cells that help to mount strong antitumour responses.

The local environment within tumours showed a similar shift, accumulating more immune-suppressive cells, including Ly6Chi monocytes, M2-like F4/80+ MHCIIlo macrophages, and regulatory T cells, that shield cancer from immune attack.

Further experiments showed that these immune changes were long-lasting. Ischaemia not only altered the expression of hundreds of genes, shifting immune cells into a more cancer-tolerant state, but also reorganised the structure of chromatin, the protein scaffolding that controls access to DNA. This made it harder for immune cells to activate genes involved in fighting cancer.

“Our results reveal a direct mechanism by which ischemia drives cancer growth, reprogramming stem cells in ways that resemble aging and promote immune tolerance,” says first author Alexandra Newman, PhD, a postdoctoral scholar in Dr Moore’s lab. “These findings open the door to new strategies in cancer prevention and treatment, like earlier cancer screening for patients with peripheral artery disease and using inflammation-modulating therapies, to counter these effects.”

Moving forward, the research team hopes to help design clinical studies that evaluate whether existing inflammation-targeted therapies can counter post-ischaemic changes driving tumour growth.

Source:

Categories : Cancer ExerciseTags :

Bouts of Exercise Could Help in the Fight Against Cancer

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Photo by John Arano on Unsplash

A single bout of either resistance or high intensity interval training could help in the cancer battle, new research from Edith Cowan University (ECU) has found.

ECU PhD student Mr Francesco Bettariga found that a single bout of exercise increased the levels of myokines, a protein produced by muscles which has anti-cancer effects, and which could reduce the proliferation of cancer growth by 20 to 30 per cent.

“Exercise has emerged as a therapeutic intervention in the management of cancer, and a large body of evidence exists that shows the safety and effectiveness of exercise as medicine, either during or post cancer treatment,” Mr Bettariga said, first author of the study which appears in Breast Cancer Research and Treatment.

His research with survivors of breast cancer measured myokine levels before, immediately after and 30 minutes post a single bout of either resistance of high intensity interval training and found that both sets of exercise had a resultant increase in myokine levels.

While higher levels of myokines were expected in a healthy population, post a vigorous workout, Mr Bettariga investigated whether breast cancer survivors would see the same results, given the impact that cancer treatments and cancer itself often has on the body.

“The results from the study show that both types of exercise really work to produce these anti-cancer myokines in breast cancer survivors. The results from this study are excellent motivators to add exercise as standard care in the treatment of cancer,” Mr Bettariga said.

He added that the long-term implications of elevated myokine levels should be further investigated, particularly in relation to cancer recurrence.

Further research by Mr Bettariga investigated how changes in body composition, following consistent exercise, could impact inflammation, which plays a key role in breast cancer recurrence and mortality by promoting tumour progression.

Persistent inflammation not only promotes tumour progression by influencing cell proliferation, survival, invasiveness, and metastasis, but also inhibits immune function. Given that the cancer itself and the side-effects of treatments can elevate levels of inflammatory biomarkers, survivors of breast cancer are at increased risk of cancer progression, recurrence and mortality.

“Strategies are needed to reduce inflammation which may provide a less supportive environment for cancer progression, leading to a lower risk of recurrence and mortality in survivors of breast cancer,” Mr Bettariga said.

The new research found that by reducing fat mass and increasing lean mass, through consistent and persistent exercise, cancer survivors had a better chance at reducing inflammation.

“If we are able to improve body composition, we have a better chance of decreasing inflammation because we are improving lean mass and reducing fat mass, which is responsible for releasing anti and pro-inflammatory markers,” Mr Bettariga said.

Unfortunately, quick fixes to reduce fat mass would not have the same beneficial effects, Mt Bettariga stressed.

“You never want to reduce your weight without exercising, because you need to build or preserve muscle mass and produce these chemicals that you can’t do through just diet alone.”

Source: Edith Cowan University

Categories : Cancer ImmunologyTags :

Decoding How Immune Cells Communicate in Autoimmune Disease and Cancer

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Squamous cancer cell being attacked by cytotoxic T cells. Image by National Cancer Institute on Unsplash

By measuring interactions between cells, the method offers insights into how the human body fights viral infections, how malfunctions can lead to autoimmune diseases and why immunotherapies work for some people but not others.    

A healthy immune system is trained to detect and destroy infections and cancer cells. This defence is based on a complex communication system at cellular level, in which different immune cells each perform a specialised task: recognising infectious agents, alerting other immune cells, and eliminating harmful cells or pathogens. Problems arise when communication between different cell types is disrupted, potentially leading to a variety of diseases.  

For example, cancer cells often develop strategies to specifically disrupt or circumvent the exchange of information in the immune system – this allows them to evade immune surveillance and grow unhindered. “Modern immunotherapies have fundamentally changed the treatment of certain types of cancer by restoring or specifically strengthening communication between immune cells,” explains Prof Simon Haas, one of the leaders of the study.  

Dr Daniel Hübschmann, also head of the study, adds: “However, not all patients respond equally well to these therapies and reliable methods for predicting which patients will benefit most are still lacking.”   

Decoding immune cell communication for personalised cancer therapies    

Scientists have now developed a technology that overcomes many of these hurdles through a better understanding of immune cell communication. With this method, made possible by interdisciplinary collaboration, millions of cell-cell interactions can be measured quickly and cost-effectively, both in research laboratories and in the clinic.   

The scientists are using the newly developed technology to investigate the behaviour and kinetics of immunotherapies and to gain insights into how these therapies work at the level of cell-cell interactions. They were able to show that the approach enables the prediction of individual therapy responses and can thus create a central basis for personalised immunotherapies and targeted therapy decisions.   

In addition, the researchers were able to use their new technology to visualise, in high resolution, how cells of the immune system interact with each other during viral infections and autoimmune diseases. The results allow them to develop dynamic maps of immune cell networks, illustrating for the first time how the immune defence is coordinated in different tissues.   

Together with clinical partners, the team is now working on translating these findings from research into practice, for example to better predict treatment success and utilise immunotherapies in a more personalised manner.   

The study was published in Nature Methods.  

Source: Queen Mary University London

Categories : CancerTags :

Pembrolizumab–Axitinib Duo Extends Survival in Advanced Kidney Cancer

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Photo by Robina Weermeijer on Unsplash

A two-drug combination for treating advanced kidney cancer had sustained and durable clinical benefit in more than five years of follow-up, according to a study published August 1 in Nature Medicine. 

The study reports final clinical data and biomarker analyses from the Phase 3 KEYNOTE-426 trial, which compared the drug combination pembrolizumab plus axitinib versus the single drug sunitinib for patients with previously untreated advanced clear cell renal cell carcinoma, the most common type of kidney cancer.

“KEYNOTE-426 was the first trial to combine a PD-1 inhibitor immunotherapy (pembrolizumab) with a VEGF receptor inhibitor antiangiogenic drug (axitinib) in the first-line setting for advanced renal cell carcinoma. It therefore has the longest follow-up duration among the various trials comparing these types of drug combinations,” said Brian Rini, MD, a medical oncologist at Vanderbilt-Ingram Cancer Center, Professor of Medicine and the study’s lead and corresponding author. 

Immunotherapy drugs like pembrolizumab stimulate the immune system to kill tumour cells. VEGF receptor inhibitors like axitinib and sunitinib block angiogenesis — the development of blood vessels that tumours need to grow and spread. Pembrolizumab plus axitinib and other immunotherapy-antiangiogenic drug combinations are now standard first-line treatments for advanced kidney cancer. 

“Before the development of antiangiogenic drugs and immunotherapies, advanced renal cell carcinoma had a very poor prognosis. These drug combinations have dramatically improved treatment options and outcomes for patients,” said Rini. 

The first interim analysis of outcomes from KEYNOTE-426, published Feb. 16, 2019, in the New England Journal of Medicine, demonstrated that trial participants treated with pembrolizumab plus axitinib had longer overall and progression-free survival, and higher objective response rates compared to those taking sunitinib. The median follow-up was 12.8 months. 

Now, with a median follow-up of 67.2 months, the current analysis confirms and extends the interim analysis and provides valuable information about biomarkers that could help guide treatment decisions. 

The study in Nature Medicine reports that pembrolizumab plus axitinib had longer overall survival (47.2 months versus 40.8 months for sunitinib) and longer progression-free survival (15.7 months versus 11.1 months for sunitinib). The objective response rate was 60.6% for pembrolizumab plus axitinib and 39.6% for sunitinib. 

The researchers reported a variety of associations between the expression of biomarkers and outcomes (overall survival, progression-free survival, objective response rate). The biomarkers they evaluated included an 18-gene T-cell-inflamed expression profile, angiogenesis signature, and PD-1 ligand expression. 

“There is an unmet need for biomarkers that are predictive of patient outcomes following treatment with available first-line therapies for advanced renal cell carcinoma,” Rini said. “Although our analysis showed potential clinical utility of some RNA signatures in identifying patients who are likely to benefit the most from each treatment, further prospective clinical studies are needed.” 

Pembrolizumab plus axitinib is a first-line treatment option for patients with advanced renal cell carcinoma regardless of biomarker subtypes, he noted. 

Source: Vanderbilt University Medical Center

Categories : CancerTags :

When Should Preventive Mastectomy be Offered in High Breast Cancer Risk?

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Photo by National Cancer Institute on Unsplash

More women at higher risk of breast cancer should be offered a mastectomy, according to researchers at Queen Mary and London School of Hygiene and Tropical Medicine.

A new analysis, published in JAMA Oncology, has found that the surgical technique was a cost-effective way of reducing the likelihood of developing breast cancer compared to breast screening and medication. Current guidelines on who is offered mastectomy may need to be revised to reflect these new findings. 

Clinicians currently use personalised risk prediction models which combine genetic and other data to identify those women who are at a higher risk of developing breast cancer (BC). Subsequent treatment options – including mammograms, MRI screening, surgery, and medication – are then offered dependent on each woman’s level of risk. 

Risk reducing mastectomy (RRM) is recommended for women at high risk, but in practice this surgery is only clinically offered to those carrying faults (called pathogenic variants) in genes that are known to increase the likelihood they will develop the disease (BRCA1/ BRCA2/ PALB2 PV). 

Professor Ranjit Manchanda from Queen Mary University of London, Dr Rosa Legood from London School of Hygiene and Tropical Medicine, along with colleagues from Manchester University and Peking University created a new economic evaluation model to accurately predict the level of risk that would make RRM a more cost-effective treatment. 

For their model, researchers used guidelines from the National Institute for Health and Care Excellence (NICE) to determine whether a treatment is considered cost-effective. Their model showed that mastectomy was a cost-effective treatment for women aged 30 or above who have a lifetime breast cancer risk greater than or equal to 35%. Offering RRM to women in this cohort could potentially prevent 6,500 of the 58,500 cases of breast cancer that are diagnosed every year in the UK. 

Professor Manchanda, Professor of Gynaecological Oncology at Queen Mary and  Consultant Gynaecological Oncologist, said: “We for the first time define the risk at which we should offer RRM. Our results could have significant clinical implications to expand access to mastectomy beyond those patients with known genetic susceptibility in high penetrance genes- BRCA1/ BRCA2/ PALB2 – who are traditionally offered this. This could potentially prevent can potentially prevent ~6500 breast cancer cases annually in UK women. We recommend that more research is carried out to evaluate the acceptability, uptake, and long-term outcomes of RRM among this group”.. 

Dr Legood, Associate Professor in health economics at the London School of Hygiene & Tropical Medicine, said: “Undergoing RRM is cost-effective for women 30-55 years with a lifetime breast cancer risk of 35% or more. These results can support additional management options for personalized breast cancer risk prediction enabling more women at increased risk to access prevention.”  

Dr Vineeth Rajkumar, Head of Research at Rosetrees, said: “Rosetrees is delighted to fund this truly groundbreaking research that could have a positive impact on women worldwide.” 

The researchers used data from women aged between 30 and 60 with varying lifetime breast cancer risks between 17% and 50%, and who were either undergoing RRM or receiving screening with medical prevention according to currently used predictive models. 

NICE deems a treatment cost-effective if it typically brings one additional year of health for no more than £20 000–£30 000 per patient (known as the ‘willingness to pay’ threshold, or WTP). The researchers’ model used a threshold of £30 000/Quality Adjusted Life Year. 

Source: Queen Mary University London