Tag: cancer treatment

Categories : CancerTags :

Unique Genetic Pattern can Predict Severe Side Effects of Melanoma Immunotherapy

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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 : Cancer ExerciseTags :

Physical Exercise Concomitant with Chemotherapy Reduces Nerve Damage

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Photo by Mikhail Nilov

Many cancer medications, from chemotherapy to modern immunotherapies, attack the nerves as well as the tumour cells. Some therapies, such as oxaliplatin or vinca alkaloids, leave 70 to 90% of patients complaining of pain, balance issues, or feelings of numbness, burning or tingling. These symptoms can be very debilitating. They can disappear following cancer treatment, but in around 50% they become chronic. Specialists call it chemotherapy-induced peripheral neuropathy, or CIPN for short.

A research team led by sports scientist Dr Fiona Streckmann from the University of Basel and the German Sport University Cologne has now shown that specific exercise, concomitant to cancer therapy, can prevent nerve damage in many cases. The researchers have reported their findings in JAMA Internal Medicine.

Exercise alongside chemo

The study involved 158 cancer patients, both male and female, who were receiving treatment either with oxaliplatin or vinca-alkaloids. The researchers divided the patients at random into three groups. The first was a control group, whose members received standard care. The other two groups completed exercise sessions twice a week for the duration of their chemotherapy, with each session lasting between 15 and 30 minutes. One of these groups carried out exercises that focused primarily on balancing on an increasingly unstable surface. The other group trained on a vibration plate.

Regular examinations over the next five years showed that in the control group around twice as many participants developed CIPN as in either of the exercise groups. In other words, the exercises undertaken alongside chemotherapy were able to reduce the incidence of nerve damage by 50 to 70%. In addition, they increased the patients’ subjectively perceived quality of life, made it less necessary to reduce their dose of cancer medications, and reduced mortality in the five years following chemotherapy.

The participants receiving vinca-alkaloids and performing sensorimotor training, had the largest benefit. 

Ineffective medications

A lot of money has been invested over the years in reducing the incidence of CIPN, explains Streckmann. “This side effect has a direct influence on clinical treatment: for example, patients may not be able to receive the planned number of chemotherapy cycles that they actually need, the dosage of neurotoxic agents in the chemotherapy may have to be reduced, or their treatment may have to be terminated.”

Despite the investments made, there is no effective pharmacological treatment to date: various studies have shown that medications can neither prevent nor reverse this nerve damage. However, according to the latest estimates, USD 17 000 are spent per patient every year in the USA on treating nerve damage associated with chemotherapy. Streckmann’s assumption is that “doctors prescribe medications despite everything, because patients’ level of suffering is so high.”

Study ongoing in children’s hospitals

In contrast, the sports scientist emphasises, the positive effect of exercise has been substantiated, and this treatment is very cheap in comparison. At the moment she and her team are working on guidelines for hospitals, so that they can integrate the exercises into clinical practice as supportive therapy. In addition, since 2023 a study has been ongoing in six children’s hospitals in Germany and Switzerland (Project PrepAIR), which is intended prevent sensory and motor dysfunctions in children receiving neurotoxic chemotherapy.

“The potential of physical activity is hugely underestimated,” says Fiona Streckmann. She very much hopes that the results of the newly published study will lead to more sports therapists being employed in hospitals, in order to better exploit this potential.

Source: University of Basel

Categories : CancerTags :

Why are Some Cancers Resistant Even Before the First Treatment?

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

In cancer, it is well known that small numbers of drug-resistant cells likely exist in tumours even before they’re treated. In something of a paradox, before treatment, these mutants have been repeatedly shown to have lower fitness than the surrounding ancestor cells from which they arose. It leads to a scenario that seems to break Darwin’s rules. Why is it that these least-fit cells survive?

In a new study published in PRX Life, researchers at Case Western Reserve University and Cleveland Clinic reveal a fascinating discovery: interactions between these mutants and their ancestors, like two species in an ecosystem, may hold the key to understanding this paradox.

Their findings suggest these ecological interactions play a pivotal role in reducing the costs of resistance, providing a path to survival for preexisting resistance. And not just in lung cancer, but across various biomedical contexts where drug resistance is a challenge, including other cancers, pathogens and even parasites.

The study

Combining computer simulations and analytical results, the study establishes a mathematical framework to examine the impact of these ecological interactions on the evolutionary dynamics of resistance.

“This is a really exciting finding because it settles some fundamental disagreements between classical population genetics and theoretical ecology,” said the study’s principal investigator Jacob Scott, staff physician-scientist at Cleveland Clinic and an associate professor of physics and medicine at Case Western Reserve.

The study also highlights the clinical relevance of these findings by genetically engineering common resistance mechanisms observed in non-small-cell lung cancer, a disease notorious for preexisting resistance to targeted therapies.

Each genetically engineered cancer cell line experienced a benefit from being with its ancestor, in the group’s evolutionary game assay when cultured with their treatment sensitive ancestor, just as the new theory predicted, bringing closure to the paradox.

“Our findings offer an attractive new hypothesis for why treatment resistance is so common: The resistant cells are saved from extinction by the other cells surrounding them through an ecological mechanism,” said Jeff Maltas, the study’s lead author and a post-doctoral fellow at Case Western Reserve. “These results provide a novel treatment strategy: designing treatments that disrupt the ecological interaction that allows resistance to gain a foothold in the first place, rather than developing new drugs for increasingly resistant populations.”

The hope is that this multidisciplinary research may lead to innovative approaches to fighting cancer and infectious diseases, the researchers said.

Source: Case Western Reserve University

Categories : CancerTags :

Study Finds no ‘Participation Effect’ Benefit for Patients in Cancer Trials

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Photo by Tima Miroshnichenko on Pexels

Cancer patients who participate in clinical trials hoping for better outcomes fare no better than those who do not, when setting aside the new treatment’s effect, according to the results of a study published in the Journal of the American Medical Association. The analysis found that while overall, trials had a positive benefit, this effect diminished after accounting for various factors common to trial participants such as being younger. Evidence of publication bias was also uncovered.

Participation in a clinical trial may confer a survival benefit to cancer patients is known as a trial effect, and results from access to effective new therapies (the treatment effect), but it is also thought that a trial’s closer monitoring provides a distinct benefit as well (the participation effect). The treatment effect only applies if the treatment proves to be effective, while the participation effect should apply regardless of treatment effect. But the evidence for the participation effect has been conflicting. A pair of reviews, one conducted in 2001 and the other in 2004, found no evidence of a participation effect.

The researchers therefore sought to account for biases and confounding in differences between routine care patients and trial patients. A search was performed for studies comparing survival outcomes for the two groups between January 1 2000 and August 31 2022, which turned up 12 791 records. After screening for eligibility and duplicates, this yielded 39 studies (85 comparisons) for analysis. These comparisons involved haematologic (21%), breast (16%), lung (14%), central nervous system (7%), prostate (7%), and pancreatic cancers (5%), as well as melanoma (6%). The remaining 24% consisted of bladder, cervical, colorectal, oesophageal, gastric, head and neck, kidney, ovarian, and solid mix tumours. One-third of the comparisons involved advanced or metastatic cancer.

Initially, the meta-analysis revealed a statistically significant overall survival benefit for trial participants (HR [hazard ratio], 0.76) when all studies were pooled without regard to their design or quality. But in study subsets matching trial participants and routine care patients for eligibility criteria, the survival benefits diminished (HR, 0.85). Finally, the survival benefit disappeared when only high-quality studies were pooled (HR, 0.91). They also disappeared when estimates were adjusted for potential publication bias (HR, 0.94).

Further analysis (using funnel plots and Egger’s regression test) indicated there was a publication bias against studies which lacked a participation effect.

In an accompanying editorial, Wilson et al. note that the participation effect explains that, “Patients in trials are generally younger, fitter, have fewer comorbidities, and come from higher socioeconomic groups; this enrollment bias largely explains the participation effect. The implications of this finding are important for understanding how trials are often viewed in clinical practice. The participation effect is often used to promote the view that “a clinical trial is the best treatment option, ‘but this may be a false narrative.”

Corresponding author Jonathan Kimmelman, PhD concluded: “Our findings provide reassurance that inability to enroll in a cancer trial doesn’t disadvantage a patient, at least in terms of survival. Our findings can help patients (and physicians) focus their consent discussions on the most relevant and evidence-based benefits of trial participation: the prospects of advancing the care of future patients.”

Categories : CancerTags :

Implantable LED Device Uses Light to Treat Deep-seated Cancers

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Certain types of light have proven to be an effective, minimally invasive treatment for cancers located on or near the skin when combined with a light-activated drug. But deep-seated cancers, surrounded by tissue, blood and bone, have been beyond the reach of light’s therapeutic effects.

This miniature, implantable LED device fights cancer with light.

To bring light’s benefits to these harder-to-access cancers, engineers and scientists at the University of Notre Dame have devised a wireless LED device that can be implanted. In combination with a light-sensitive dye, the device not only destroys cancer cells, but also rallies the immune system’s cancer-targeting response. The research was published in Photodiagnosis and Photodynamic Therapy.

“Certain colours of light penetrate tissue deeper than other ones,” said Thomas O’Sullivan, associate professor of electrical engineering and co-author on the paper. “It turns out that the kind of light – in this case green – that doesn’t penetrate as deeply has the capability of producing a more robust response against the cancer cells.”

Before the light can be effective in destroying cancer cells, a dye with light-absorbing molecules must be administered to the cells. The device turns on, the dye transfers the light into energy and that energy makes the cells’ own oxygen toxic – in effect, turning the cancer cells against themselves.

While other treatments also weaponise the cells’ own oxygen, this device causes a particularly serendipitous form of cell death.

“Working together, biochemistry graduate student Hailey Sanders and electrical engineering graduate student SungHoon Rho perceptively noted that the treated cells were swelling, which is the hallmark of a kind of cell death, pyroptosis, that’s particularly good at triggering the immune response,” said Bradley Smith, the Emil T. Hofman Professor of Science and co-author on the paper.

“Our goal is to induce just a little bit of pyroptotic cell death, which will then trigger the immune system to start attacking the cancer.”

In future studies, the device will be used in mice to see whether the cancer-killing response initiated in one tumour will prompt the immune system to identify and attack another cancerous tumour on its own.

O’Sullivan noted that the device, which is the size of a grain of rice, can be injected directly into a cancerous tumour and activated remotely by an external antenna. The goal is to use the device not only to deliver treatment but also to monitor the tumour’s response, adjusting signal strength and timing as needed.

Source: University of Notre Dame

Categories : CancerTags :

Chemo Drug may Cause Significant Hearing Loss in Longtime Cancer Survivors   

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Photo by Brett Sayles

An interdisciplinary study led by researchers at the University of South Florida and Indiana University has uncovered significant findings on the long-term effects of one of the most common forms of chemotherapy on cancer survivors.

Published in JAMA Oncology, the study tracked a cohort of testicular cancer survivors who received cisplatin-based chemotherapy. The team followed the patients for an average of 14 years, revealing that 78% experience significant difficulties in everyday listening situations, negatively impacting their quality of life. This collaborative research is the first to measure real-world listening challenges and hearing loss progression in cancer survivors over a long period of time.

“It’s important that we understand the real-world effects of patients’ sensory problems and if we can understand that, then we can develop better therapeutic strategies and preventive measures to improve the long-term quality of life for cancer survivors,” said Robert Frisina, distinguished university professor and chair of the USF Department of Medical Engineering.

Cisplatin is commonly used in chemotherapy treatments for a variety of cancers, including bladder, lung, neck and testicular. It is administered intravenously and affects various parts of the body. However, the ears are particularly vulnerable as they have little ability to filter out the drug, causing it to become trapped. This leads to inflammation and the destruction of sensory cells that are critical for coding sound, causing permanent hearing loss that can progressively get worse well after cisplatin treatments are completed.

Lead author Victoria Sanchez, associate professor in the USF Health Department of Otolaryngology Head & Neck Surgery, said that despite the known risks, there’s a nationwide lack of routine hearing assessments for patients undergoing chemotherapy. “Most patients still do not get their hearing tested prior to, during or after chemotherapy. Our study highlights the need for regular auditory evaluations to manage and mitigate long-term hearing damage.”

The research team found higher doses of cisplatin led to more severe and progressing hearing loss, especially in patients with risk factors, such as high blood pressure and poor cardiovascular health. They also experienced increased difficulty hearing in common environments, such as a loud restaurant.

“It will be critically important to follow these patients for life. Their current median age is only 48 years, and eventually they will enter the years at which age-related hearing loss also begins to develop,” said Dr. Lois B. Travis, Lawrence H. Einhorn Professor of Cancer Research at Indiana University School of Medicine and a researcher at the IU Melvin and Bren Simon Comprehensive Cancer Center. This research is part of The Platinum Study, an ongoing research effort led by Dr. Travis and funded by the National Cancer Institute to study cisplatin-treated testicular cancer survivors.

The hope is that this study will inspire further investigation into alternative chemotherapeutic protocols and preventive measures, such as FDA-approved drugs to prevent or reduce hearing loss.

“This research gives oncologists the information they need to explore alternative treatment plans that could reduce the long-term side effects, such as altering the dosages and timing of the cisplatin in the treatment, when that could be an appropriate option,” Frisina said.

Innovative solutions, such as Pedmark, a new FDA-approved injection that mitigates cisplatin-induced hearing loss in children, represent promising steps forward, according to Frisina.

“We want to protect our hearing or treat a hearing loss if hearing damage occurs,” Sanchez said. “Hearing allows us to connect to the world we love. Staying connected through conversations with family and friends, enjoyment of music and entertainment, staying safe and finding pleasure in our vibrant surroundings. Promoting optimal hearing for overall wellness is essential for healthy living.”

According to the American Cancer Society, in addition to cisplatin, other platinum chemotherapy drugs, such as carboplatin, cause damage to the cochlea in the inner ear and lead to hearing loss. The risk of damage is greater with higher doses of chemotherapy.

Source: University of San Francisco

Categories : CancerTags :

Malignant Melanoma Resists Treatment by Subverting Immune Cells

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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 General InterestTags :

Years after His Passing, Researcher’s Cancer Target Discovery Bears Fruit

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Some of the final work of a late University of Virginia School of Medicine scientist has opened the door for life-saving new treatments for solid cancer tumours, including breast cancer, lung cancer and melanoma.

Prior to his sudden death in 2016, John Herr, PhD, had been collaborating with Craig L. Slingluff Jr, MD, to investigate the possibility that a protein recently discovered at Herr’s lab could be a viable cancer treatment target.

Eight years of research has borne that idea out: Herr’s research into the SAS1B protein could lead to “broad and profound” new treatments for multiple cancers, many of which are very difficult to treat, Slingluff reports in a new scientific paper in the Journal for ImmunoTherapy of Cancer. Herr is listed as a senior author on the paper.

“John was very excited about this protein SAS1B to be a valuable new target on human cancers, and I am delighted that our findings together further support his hope to make such a difference,” said Slingluff, a surgical oncologist and translational immunologist at UVA Health and the UVA School of Medicine. “The work we published included work done by Dr Herr and his team over a period of years, as well as our subsequent work together; so, I am glad that the journal agreed with our request to include John as a senior author.”

Promising New Cancer Target

Herr’s lab was not originally focused on cancer – he was the head of UVA’s Center for Research in Contraceptive and Reproductive Health. In that role, he developed the first home fertility test for men, SpermCheck, which is available in pharmacies across the country. But his discoveries about the SAS1B protein found in developing eggs in women could pave the way for new cancer immunotherapies.

While SAS1B is found inside female reproductive cells called oocytes, it is also found on the surface of many different solid cancer cells, Slingluff’s new research verifies. Importantly, it did not appear on the surface of any of the other normal cells Slingluff’s laboratory tested. That suggests that doctors may be able to develop use antibody-based immunotherapy – such as antibody-drug conjugates or CAR T-cell therapy, a strength of UVA Health – to attack the cancer cells while sparing healthy tissue.

“Selectively targeting SAS1B has the potential to have broad and profound impact on the treatment, and therefore reduction in mortality, of multiple malignancies,” Slingluff and his colleagues write in their new paper.

While much more work needs to be done, the new findings are promising. If the approach is successful, it could be a big step forward in cancer care. Many solid-organ cancers are extremely difficult to treat, and patients often have few good treatment options, Slingluff notes.

“Immune therapy is revolutionising treatment of human cancers,” Slingluff said. “But some cancers have been particularly resistant to immune therapy because of the lack of good targets on those cancers. We hope that this work that John Herr started will bring new hope to patients with those cancers.”

Source: University of Virginia Health System

Categories : Cancer NeurologyTags :

New Drug Shows Promise for Treating Rare and Aggressive Gliomas

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MRI scan showing brain cancer. Credit: Michelle Monje, MD, PhD, Stanford University

An experimental drug may provide a new treatment option for some patients with rare incurable brain tumours, according to an analysis published in the Journal of Clinical Oncology.

Diffuse midline gliomas are diagnosed in about 800 people per year in the U.S., according to the Centers for Disease Control and Prevention.

A subset of particularly aggressive diffuse midline gliomas are caused by a H3 K27M mutation and the only effective treatment is radiation, as the location of the tumour in the brain makes surgery difficult. Even with radiation, relapse is virtually inevitable and more than 70% of patients with this subtype of brain tumour die from the cancer, according to the National Institutes of Health.

In the study, investigators analysed the results of five previous clinical trials testing the effectiveness of dordaviprone, an experimental drug which works by blocking a certain protein in tumours with the mutation.

The study included results from 50 patients (including four children) with H3 K27M–mutant diffuse midline gliomas and found that 30% of patients responded well to the drug. The most common side effect reported was fatigue, according to the study.

Now, the researchers are launching a trial at Northwestern Medicine hospitals to investigate the drug’s effectiveness in newly diagnosed patients.

Source: Northwestern University

Categories : CancerTags :

New Trial Flips the Script for Hormonal Treatment of Breast Cancer

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Photo by National Cancer Institute

For decades, hormonal treatment of breast cancer has been going in one direction: blocking oestrogen. Now, a global study has discovered there may be another, less toxic way to defeat the most common form of breast cancer. The results, published in The Lancet Oncology, showed that the androgen receptor (AR) agonist enobosarm, is effective against oestrogen receptor-positive (ER+) breast cancer, which constitutes up to 80% of all breast cancer cases.

“The effectiveness of enobosarm lies in its ability to activate the AR and trigger a natural defence mechanism in breast tissue, thereby slowing the growth of ER+ breast cancer, which relies on the hormone oestrogen to grow and spread,” said senior co-author Professor Wayne Tilley, Director of the Dame Roma Mitchell Cancer Research Laboratories at the University of Adelaide.

“This clinical study is supported by our pre-clinical research, previously published in Nature Medicine, which established that the AR is a tumour suppressor in both normal breast tissue and ER+ breast cancer.”

Along with investigators from the University of Adelaide and Dana-Farber Cancer Institute (DFCI) in Boston, USA, the international study also included researchers from the University of Liverpool in the UK and other experts around the world.

The team assessed enobosarm’s efficacy and safety in 136 postmenopausal women with advanced or metastatic ER-positive, HER2-negative breast cancer.

Enobosarm showed significant anti-tumour activity and was well-tolerated by patients, without adversely affecting their quality of life or causing masculinising symptoms.

This discovery represents the first advancement in hormonal treatment of ER+ breast cancer in decades and offers a promising new oral treatment strategy for the most prevalent form of breast cancer.

The new hormonal strategy differs from the existing standard-of-care hormonal treatments, which have been around for decades and involve suppressing oestrogen activity in the body or inhibiting the ER.

Although successful initially, treatments targeting ER can cause severe side effects and treatment-resistant progression of the disease is common.

“Our findings are very promising. They demonstrate that stimulating the androgen receptor pathway with enobosarm can be beneficial,” said senior co-author and study Principal Investigator Dr Beth Overmoyer from DFCI.

“This is the first time a non-oestrogen receptor hormonal treatment approach has been shown to be clinically advantageous in ER+ breast cancer. The study supports further investigation of enobosarm in earlier stages of breast cancer as well as in combination with targeted therapies, such as ribociclib, a CDK 4/6 inhibitor.”

estrogen to grow and spread,” said senior co-author Professor Wayne Tilley, Director of the Dame Roma Mitchell Cancer Research Laboratories at the University of Adelaide.

“The data strongly encourages more clinical trials for AR-stimulating drugs in treating AR-positive and ER-positive breast cancer. The fact that this drug is well-tolerated also opens possibilities for its use in breast cancer prevention,” said co-author Dr Stephen Birrell, a clinical affiliate of the University of Adelaide.

Source: University of Adelaide