Positive Health Online

Promising Treatment for Incurable Prostate Cancer

A new study reveals a potential breakthrough in combating aggressive prostate cancer

Researchers from Flinders University and University of South Australia have unveiled a promising new strategy that could be used to treat the most aggressive forms of prostate cancer. This groundbreaking study, published in British Journal of Cancer,[1] explores the role of a novel drug, CDKI-73, to tackle drug-resistant prostate cancer that defies conventional therapies.

Prostate cancer is the most commonly diagnosed cancer in Australian men and causes more than 3,300 deaths each year. The disease frequently evolves into aggressive forms that do not respond to standard hormone therapies.

Despite this, prostate cancer remains a sensitive and often under-discussed topic.

The study, led by Associate Professor Luke Selth from Flinders University and Professor Shudong Wang from University of South Australia, investigated the potential of targeting a protein called Cyclin-Dependent Kinase 9 (CDK9), which plays a crucial role in the growth and survival of prostate cancer cells. More specifically, the researchers tested whether an inhibitor of CDK9, CDKI-73, could overcome the cancer's resistance to current treatments.

“Our research demonstrates that CDKI-73 potently blocks the growth of prostate cancer, even aggressive subtypes of the disease that are resistant to current treatments,” says Associate Professor Selth.

“Importantly, CDKI-73 targets cancer cells specifically without harming normal cells and its potential as an oral capsule makes it an attractive treatment option.”

Using advanced technologies, the study examined the effects of CDKI-73 using an array of prostate cancer models, including patient tumour samples, which revealed not only the effectiveness of the inhibitor but also provided new insights into its mode of action.

“This study represents a significant step forward in understanding the role of CDK9 in aggressive prostate cancer,” adds Associate Professor Selth.

“Having said that, we still need to do a lot more work to fully understand the potential of CDK9 inhibitors and to deliver a new treatment for patients.”

CDKI-73 is currently being investigated in Phase 2 clinical trials in patients with relapsed and therapy-resistant acute myeloid leukaemia, an aggressive blood cancer.

“This study demonstrates that CDKI-73 is a promising candidate for treating solid tumours such as prostate cancer,” says Professor Wang, who developed CDKI-73. 

“Our proof-of-principle study is an important step towards future clinical trials and these findings will inform future studies in the use and efficacy of CDKI-73 as a prostate cancer treatment,” adds Professor Wang.

Reference

1. Razia Rahman, Muhammed H. Rahaman et al. “CDK9 inhibition inhibits multiple oncogenic transcriptional and epigenetic pathways in prostate cancer” British Journal of Cancer  DOI: 10.1038/s41416-024-02810-8.  2024.

Acknowledgements

This study was supported by funding from Cancer Australia, The Hospital Research Foundation, the Victorian Cancer Agency, National Institutes of Health, Movember, National Breast Cancer Foundation, Cancer Council SA, Flinders Foundation, EJ Whitten Foundation, Peter and Lyndy White Foundation and Aucentra Therapeutics Pty. Ltd.

During September, Flinders Foundation is recognising Prostate Cancer Awareness Month with a special research forum - https://flindersfoundation.org.au/events/prostate-cancer-forum

 Further Information

Associate Professor Luke Selth, College of Medicine and Public Health, Flinders University

Tel: +61 8 74219889 Email: luke.selth@flinders.edu.au

Prof Shudong Wang, Drug Discovery and Development, Clinical and Health Sciences, University of South Australia. Email: shudong.wang@unisa.edu.au

Sally Lauder, Media Advisor, Flinders University  

Tel: +61 08 8432 4288 Mob: +61 (0)410 248 446  Email: sally.lauder@flinders.edu.au 

Web: www.news.Flinders.edu.au Twitter: @FlindersUniNews 

 Original Media Contact

Yaz Dedovic yaz.dedovic@flinders.edu.au

Do Cancer and Cancer-Related Treatments Increase Cardiovascular Disease Risk in Older Cancer Survivors? 

A study based on clinical trial data found higher risks of stroke, heart attack, and hospital admission for heart failure in older cancer survivors. In the analysis published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society, chemotherapy was also linked to elevated rates of these conditions.  Although advances in treatment have led to decreased cancer mortality over the past decade, the growing numbers of cancer survivors may experience long-term effects of cancer and anticancer therapies. For example, the heart may be especially vulnerable to inflammation triggered by cancer and toxic effects from chemotherapy and radiation. 

To investigate cardiovascular disease incidence in older cancer survivors and the impact of specific cancer treatments on heart health, a team led by Monash University’s Suzanne Orchard, PhD analyzed information from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, which included adults aged 70 years and older who were living in Australia and the United States.[1] 

Other studies have observed cerebrovascular diseases such as stroke and heart attacks following cancer treatment, but to the authors’ knowledge, this is the first that has explored the effects of individual treatment modalities on different cancer types, along with the impact of aspirin on rates of cerebrovascular diseases.

Of the 15,454 participants, 1,392 developed cancer over an average follow-up of 4.6 years. When the researchers assessed which participants experienced a cardiovascular disease event including stroke, heart attack, or hospital admission for heart failure, they found that the rate was twice as high in those who developed cancer compared with those who were cancer-free, at 20.8 versus 10.3 events per 1,000 person-years. (This means there would be an average of 20.8 and 10.3 cardiovascular disease events among 1,000 people over one year in the respective groups.) This elevated risk – which was seen across the different cardiovascular outcomes – remained even after accounting for traditional cardiovascular disease risk factors.

The incidence of cardiovascular disease events was greatest in patients with metastatic, blood, and lung cancers. Also, chemotherapy was associated with a 2-times higher risk of cardiovascular disease events. 

Analyses were inconclusive regarding other systemic therapies such as hormonal therapy, targeted therapy, immunotherapy, and radiation therapy – although thoracic radiation is known to confer an elevated risk. Aspirin (the clinical trial intervention in the trial) did not impact cardiovascular disease incidence.

Dr Orchard stressed the importance of early screening and preventive measures as early as possible and the need for continued research to further protect cancer survivors’ cardiovascular health. 

“Our research contributes to the growing body of work indicating that cancer- and treatment-related cardiovascular disease is a very real risk in cancer survivors,” she said. “Cardiovascular disease can have a significant impact on both quality of life and survival for patients with cancer. Fortunately, with early screening and preventative measures, some of the cancer-related risks can be mitigated.”

Reference

1. “Cardiovascular disease and stroke following cancer and cancer treatment in older adults.” Jaidyn Muhandiramge, John R. Zalcberg, Erica T. Warner, Galina Polekhina, Peter Gibbs, G J. van Londen, Wendy B. Bernstein, Finlay Macrae, Andrew Haydon, Jeanne Tie, Jeremy L. Millar, Victoria J. Mar, Lucy Gately, Andrew Tonkin, Leslie Ford, Asad Umar, Andrew T. Chan, Robyn L. Woods, and Suzanne G. Orchard. CANCER; Published Online: (DOI: 10.1002/cncr.35503). September 23, 2024.  https://doi.org/10.1002/cncr.35503

Author Contact

Cheryl Critchley of Monash University Marketing, Admissions, and Communications, at cheryl.critchley@monash.edu or +61 (0) 477 571 442. 

Media Contact and Further Information

Sara Henning-Stout shenningst@wiley.com

Copyright Information

The information contained in this release is protected by copyright. Please include journal attribution in all coverage. A free abstract of this article will be available via the CANCER Newsroom upon online publication. For more information or to obtain a PDF of any study, please contact: Sara Henning-Stout, newsroom@wiley.com 

About the Journal

CANCER is a peer-reviewed publication of the American Cancer Society integrating scientific information from worldwide sources for all oncologic specialties. The objective of CANCER is to provide an interdisciplinary forum for the exchange of information among oncologic disciplines concerned with the etiology, course, and treatment of human cancer. CANCER is published on behalf of the American Cancer Society by Wiley and can be accessed online. Follow CANCER on X@JournalCancer and Instagram @ACSJournalCancer, and stay up to date with the American Cancer Society Journals on LinkedIn.

 About Wiley 

Wiley is a knowledge company and a global leader in research, publishing, and knowledge solutions. Dedicated to the creation and application of knowledge, Wiley serves the world’s researchers, learners, innovators, and leaders, helping them achieve their goals and solve the world's most important challenges. For more than two centuries, Wiley has been delivering on its timeless mission to unlock human potential. Visit us at Wiley.com. Follow us on Facebook, X, LinkedIn and Instagram.

New Study Reveals Breakthrough in Early Melanoma Detection

Tumour-specific antibodies able to detect melanoma in its earliest stages, new study shows

Innovative research has unveiled promising advancements in melanoma detection, which could significantly enhance diagnosis and prognosis by identifying the disease at its earliest, most treatable stages.[1]

This new method, presented today at the European Academy of Dermatology and Venereology (EADV) Congress 2024, uses tumour-specific profiling to detect antibodies unique to stage I and II melanoma patients.

Melanoma, a skin cancer with a high mutation rate,[2]produces immunogenic markers that trigger an immune response, resulting in the production of antibodies against cancer-testis antigens (CTAgs).[3] These CTAgs lead to the production of specific antibodies that can act as early diagnostic and prognostic markers for melanoma.

In this study, a cancer array was used to analyse and compare blood samples from 199 patients with stage I and II melanoma and 38 healthy donors recruited through Lifeblood. Blood samples were collected at initial diagnosis and within 30 days of curative-intent surgery.

Specific IgG antibodies against three tumour antigens were identified as promising diagnostic biomarkers for early-stage melanomas, with area under the curve (AUC) values ranging from 0.857 to 0.981 in the discovery cohort and from 0.824 to 0.985 in the internal validation cohort.

Of the three identified markers, one showed an AUC value of 0.9805 in the discovery cohort,* with 98% sensitivity and 76% specificity, and 0.9846 in the validation cohort, with 99% sensitivity and 82% specificity.

“These results indicate that 99% of melanoma patients in the validation cohort were positive for this marker, while 82% of healthy individuals were correctly identified as negative using the recommended threshold,” explains Dr Cristina Vico-Alonso, lead researcher from the Victorian Melanoma Service, Melbourne, Australia. “While 18% of healthy individuals were incorrectly identified as positive for this marker, combining it with the other two markers into a multi-parameter signature does, however, help improve accuracy.”.

Based on the validation data, only 1% of melanoma patients would have a negative test for this top marker, suggesting that a negative result is highly indicative of the absence of melanoma.

“It is important to note, though, that this cohort included healthy individuals with no prior or current cancers and excluded individuals at high risk of developing melanoma,” says Dr Vico-Alonso. “Further testing in a real-world cohort is necessary to determine if these findings hold true when confounding factors, such as comorbidities, are considered." Data from a second, external validation cohort – to be presented at the congress – may add further insights on this.

“One significant advantage of this cancer array is its tumour-agnostic nature,” Dr Vico-Alonso adds. “CTAgs are expressed in many solid tumours, making the diagnostic signature identified here applicable beyond melanoma. However, the specific cognate antigen combination remains unique to melanoma compared to other solid tumours.”

"We are currently using the cancer array to identify candidates for a pan-cancer diagnostic test, initially focusing on melanoma, lung, bowel and pancreatic cancers," Dr Vico-Alonso shares. "In previous research, we identified a unique signature of antigens in advanced melanoma patients associated with more aggressive disease or metastases. Recently, we also identified another distinct antigen signature that differentiates between stage III melanoma patients who experienced recurrence and those who did not."

The early detection of melanoma remains a pressing challenge in oncology, with this research representing a significant step forward, offering hope for more effective, non-invasive diagnostic tools. Critically, early detection can lead to earlier surgical and therapeutic interventions, reducing the number of patients presenting with advanced disease and improving outcomes.[4]

Dr Vico-Alonso concludes, “This method of early detection could be integrated into current melanoma screening practices to provide additional information, especially in uncertain cases, potentially avoiding unnecessary procedures.”

References

1. Vico-Alonso, C., Mar, V., Sashindanath, M., & Da Gama Duarte, J. (2024). Early detection of melanomas using circulating tumour-specific antibodies. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024.
2. Heistein, J. B., Acharya, U., & Mukkamalla, S. K. R. (2024). Malignant melanoma. In StatPearls. Treasure Island, FL: StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK470409/
3. Õunap, K., Kurg, K., Võsa, L., Maiväli, Ü., Teras, M., Planken, A., Ustav, M., & Kurg, R. (2018). Antibody response against cancer-testis antigens MAGEA4 and MAGEA10 in patients with melanoma. Oncology Letters, 16(1), 211–218. https://doi.org/10.3892/ol.2018.8684
4. Davis, L. E., Shalin, S. C., & Tackett, A. J. (2019). Current state of melanoma diagnosis and treatment. Cancer biology & therapy, 20(11), 1366–1379. https://doi.org/10.1080/15384047.2019.1640032

Key Terms Defined

* The discovery cohort is used to find promising biomarkers, while the internal validation cohort is used to confirm that these biomarkers are valid and reliable in a different group of subjects.

About the Study Author

Cristina Vico-Alonso MD is a MIR [Médico Interno Residente] – certified dermatologist currently collaborating with the Victorian Melanoma Service (The Alfred Hospital) and Monash University in Melbourne, Australia.

About EADV

Founded in 1987, EADV is a non-profit organisation with a vision to form a premier European Dermatology-Venereology Society. The Academy counts over 11,000 members from all around the globe, providing a valuable service for every type of dermatologist-venereologist professional. The EADV is dedicated to advancing patient care, education and research by providing a unique platform to bring people together and share ideas. This year, the EADV Congress will take place in Amsterdam, The Netherlands, and online from 25-28 September 2024. Find out more: https://eadv.org/congress/

Media Contact and Further Information

"EADV - Press" press@eadv.org

 European Academy of Dermatology and Venereology (EADV) Congress 2024

Concern over School And University Starters as Immunity Levels Fall Below WHOs Recommendations

As students start school and university, falling childhood vaccinations mean England no longer has the levels of population immunity recommended by WHO to prevent outbreaks. A leading expert warns Brits should be on the lookout for measles and meningitis symptoms.

A leading testing expert fears a perfect storm of infections now students have returned to schools and colleges. His warning comes as the UK’s Health Security Agency (UKHSA) says falling vaccination levels means England no longer has the levels of population immunity recommended by the World Health Organization to prevent disease outbreaks.

Leading testing expert, Dr Avinash Hari Narayanan (MBChB), Clinical Lead at London Medical Laboratory, says: ‘As many young people start university or school, Britain’s falling vaccination uptake levels are causing concern. Over the past 10 years, uptake for childhood vaccinations in England has been falling across all vaccines, including those that protect against whooping cough, measles, mumps and rubella, polio, meningitis and diphtheria.

“A combination of the impact of – unfounded – historical MMR vaccination scares, Covid lockdowns on school inoculation schedules and a fall in pre-school vaccinations has created a concerning situation. Many children and young adults are entering school or university for the first time without having had essential inoculations.

“It's timely that a new campaign is now being delivered by UKHSA, in partnership with the Department for Health and Social Care (DHSC) and NHS England. It will remind parents and carers of the risk of their children missing out on protection against serious diseases, including measles, whooping cough, meningitis, diphtheria and polio.

“However, we are already seeing the impact of the fall in vaccinations. Since autumn 2023, there have been a number of major measles outbreaks in the West Midlands, the North West and London, resulting in the highest number of cases in England since 2012.

“Two MMR jabs offer the best and safest protection against measles. If unvaccinated, children are at risk of serious illness, potentially leading to hospitalisation, lifelong complications and even death in rare cases. Ideally, children should receive one dose offered at 1 year and a second dose at 3 years 4 months. If that hasn’t happened, parents should get their children inoculated as soon as possible.

“The campaign’s urgent message is: “If children aren’t vaccinated, they’re not protected.” This went live as the new school term began, in an attempt to prevent a rise in measles cases similar to that of last October.

“Equally vital is the MenACWY vaccine. This protects against four strains of the meningococcal bacteria – A, C, W and Y – that cause meningitis and bloodstream infections (septicaemia). It’s normally offered to all pupils aged 13 to 15 years old alongside the “teenage booster” jab, which is given to increase protection against tetanus, diphtheria and polio.

“However, many students who were aged around 15 in 2021 may have missed these key jabs because of Covid school closures. This age group is now starting university. The latest MenACWY coverage data shows the vaccination rate has now fallen to 79.6%.

“It's particularly concerning, as cases of so-called “freshers’ flu” (usually caused by assorted bugs that spread quickly through the student population in the first weeks of term) can be confused with symptoms of meningitis in its early stages. Like freshers’ flu, meningitis is initially difficult to distinguish from a bad hangover or common, milder illnesses. This can also be the case with the early stages of measles or mumps.

“For students and parents concerned about the potential increase in meningitis cases, it’s important to note that anyone who was eligible but missed their teenage MenACWY vaccine can still have the jab up to their 25th birthday. The Government’s advice is: “If you are older and starting university for the first time, make sure you have had your vaccine before you enrol.”

“For anyone concerned, a general health test will provide reassurance that they are in good overall health. This can help fight new viruses and boost overall fitness levels. The healthier a person is, the better their response to a serious condition can be.

“London Medical Laboratory’s General Health Profile blood test provides people with a comprehensive check-up of their general health, including diabetes (HbA1c), gout, liver & kidney function, bone health, iron levels and a full cholesterol profile. It can be taken at home through the post, or at one of the many drop-in clinics that offer these tests across London and nationwide in over 120 selected pharmacies and health stores. For full details, see: https://www.londonmedicallaboratory.com/product/general-health

Contact and Further Information 

London Medical Laboratory’s Clinical Lead, Dr Avinash Hari Narayanan, is available to supply exclusive written comment or for interview. To contact Dr Hari Narayanan, or for more information, please email London Medical Laboratory’s Head of Public Relations, David Jinks M.I.L.T., at david.jinks@londonmedicallaboratory.co.uk.

Research Casts New Light on Effectiveness of Prevention of Weight Gain in Young Adults

An ingredient which can be added to food to make it more filling may be less effective at preventing weight gain in young people but could help them build more muscle, new research suggests.

In a new paper published in eClinicalMedicine, researchers from UK universities report on the results of a randomized trial which expands on previous tests of the effectiveness of a compound called inulin-propionate ester, or IPE, to promote weight loss and suppress appetite.[1]

IPE contains propionate, a short-chain fatty acid produced in the human body when dietary fibre is fermented by gut microbes. When propionate is introduced into the body in larger quantities than could be ingested through a normal diet in the form of IPE, it stimulates the gut to release hormones which can affect the brain to reduce feelings of hunger.

Previous research from the same team showed that older participants with a mean age of 54 who took IPE supplements actually lost weight, had lower fat mass and intra-abdominal fat, and found high-energy foods less appealing than those who took a control substance called inulin, a type of fibre.

The results of the research are part of a wider study called iPREVENT, The new study, which is longer-term than previous studies, shows some differences in the ways that younger people’s bodies reacted to IPE supplements.

Over the course of the 12-month study, 270 participants across Glasgow and London aged 20 to 40 were divided into groups consuming either IPE or inulin.

The trial revealed no significant difference in weight gain between the IPE and control groups over the course of the study. The IPE group saw no reduction in fat mass or body weight, and blood glucose levels also rose marginally in the IPE group, though within normal ranges.

However, the researchers found a significant increase in fat-free mass in the participants given IPE which wasn’t accounted for by a change in physical activity among either group.

Professor Douglas Morrison of the Scottish Universities Environmental Research Centre (SUERC) and the University of Glasgow, is one of the paper’s corresponding authors. He said: “Preventing weight gain in early life can have significant health benefits later in life – it’s better to maintain a healthy weight throughout life than to try to lose weight as an older adult, although reaching a healthy weight at any age is beneficial.

“Our previous studies had shown that older people could benefit significantly from adding IPE supplements to their diets, and we were keen to explore in this study whether the results would be similar in younger people. Increasing fat-free mass is an interesting and unexpected result which may warrant further study, because building muscle can help improve metabolic health.”

The researchers note in the paper that the results may have been affected by the Covid-19 pandemic, which occurred during the study and may have influenced the diets and lifestyles of the participants. They also highlight the possibility that the dose of IPE, which produced beneficial effects in older people, may have not had the same effect on the metabolisms of the younger participants.

Professor Gary Frost of Imperial College London, the lead investigator in London, said: “These findings highlight the complexity of weight gain prevention, particularly in younger adults, where behaviours and energy intake differ from older populations. While IPE demonstrated benefits for body composition, its impact on overall weight management appears limited, warranting further research into age-specific interventions for obesity prevention.”

Reference 

1. Increase in colonic PRopionate as a method of prEVENTing weight gain over 12 months in adults aged 20–40 years (iPREVENT): a multi-centre, double-blind, randomised, parallel-group trial. Pugh, Jennifer E. et al. eClinicalMedicine, Volume 76, 102844. October 2024.  https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00423-1/fulltext

The research was supported by funding from the Medical Research Council and NIHR.

Contact and Further Information

For more information contact Ross Barker in the University of Glasgow External Relations team at ross.barker@glasgow.ac.uk