Restorative programme helps post-cancer treatment patients regain hair, confidence, and quality of life after facing cancer
Photo by Natasha Brazil on Unsplash
The Cancer Association of South Africa (CANSA) has partnered with internationally renowned hair restoration clinic Alvi Armani South Africa, with head offices in Beverly Hills Los Angeles, to launch an initiative offering complimentary consultations and assessments to those recovering or recovered from cancer.
For many, completing cancer treatment is an experience that brings immense relief. However, it doesn’t always mark the end of the emotional journey. While chemotherapy and radiation often save lives, they can leave lasting reminders – and hair loss is among the most visible.
Cindy Pretorius, a cancer survivor who was diagnosed with basal cell carcinoma, an invasive skin cancer knows firsthand how the impact of the disease affects not just self-confidence but self-worth. After the cancer was removed, the surgery left lasting and visible scarring on her hairline. A hairline that was subsequently treated and restored through a minimally invasive hair transplant at Alvi Armani South Africa. “The team at Alvi Armani restored not only my hairline, but also my confidence,” said Pretorius.
Launching in August 2025, the initiative will offer CANSA-affiliated patients in recovery access to complimentary, in-depth, and personalised consultations. This may include scalp density and mapping assessments, as well as checks for lingering treatment effects. Where needed, survivors will receive advice and support with restorative hair treatments or transplants at Alvi Armani South Africa – offering significant financial relief and a renewed sense of hope.
“This isn’t about vanity. It’s about healing the whole person,” notes Dr Kashmal Kalan, Medical Director of Alvi Armani South Africa. “Unfortunately, even when cancer treatments end, the physical and emotional recovery continues. Many individuals in remission are confronted with reminders every time they look in the mirror and see someone who still looks like a patient, often making it difficult to reconnect with the person they were before cancer.”
For those recovering from cancer, the devastation of hair loss can continue to weigh heavily on their mental well-being. Studies show that persistent thinning, patchiness, or recession after treatment can fuel anxiety, depression, and social withdrawal. Even when remission is achieved, hair regrowth can be slow, and this gap between survival and self-image can take a heavy toll.
“Hair plays an important role in how we express identity; by restoring it, we help people feel like themselves again – more confident to re-enter public life, apply for jobs, or socialise without feeling marked by illness,” he explains.
In cases where hair loss is permanent, transplants using Alvi Armani’s minimally invasive Vitruvian or Maximus follicular unit extraction (FUE) technique may also be performed. Recognised as global leaders in hair transplant procedures, Alvi Armani’s network – spanning Beverly Hills, Salt Lake City, Phoenix, San Diego, Buenos Aires, Montevideo, and Johannesburg – all use state of the art protocols, ensuring that South African patients receive the same world-class standard of care they would get at any other Alvi Armani clinic globally.
“People who’ve overcome cancer deserve more than just a life saved. They deserve the chance to live it fully, with confidence and joy. We’re extremely proud to walk this journey with them, and to help them reclaim their full sense of self.”
Alvi Armani are committing extensive financial and medical resources to support the initiative. A patient referral and screening process is in place to ensure clinical suitability, but any CANSA-affiliated person in remission may apply directly and will be guided accordingly.
CANSA and Alvi Armani will also collaborate at national events such as CANSA Relay For Life, and the CANSA High Tea, where participants will receive expert advice on scalp health, treatment options, and realistic expectations around regrowth.
“When you’ve fought so hard to stay alive, the last thing you want is to be reminded daily of what you lost. This partnership is ultimately about giving people that final piece of the puzzle back, so they can look in the mirror and not only see what they’ve overcome, but truly see themselves again,” concludes Dr Kalan.
“At CANSA, we understand that the cancer experience doesn’t end with treatment – healing also means restoring dignity, self-confidence, and quality of life. Our partnership with Alvi Armani South Africa reflects our commitment to holistic survivorship care. By offering complimentary consultations and access to world-class restorative hair solutions, we’re helping survivors reclaim not only their appearance but also their sense of self,” says Makoma Raolane, CANSA’s Sustainability Manager.
Individuals affected by cancer who are interested in the initiative can contact Alvi Armani South Africa directly, referencing their affiliation with CANSA, to schedule a complimentary consultation.
Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health
Most men who are treated for prostate cancer according to modern guidelines have good survival rates and the majority of these men will die of causes other than prostate cancer. This is revealed in a new study from Uppsala University published in the Journal of the National Comprehensive Cancer Network.
“We were surprised by how much life expectancy affected the prognosis. This shows the importance of a thorough assessment of the general health of a man with newly diagnosed prostate cancer. The patient’s life expectancy has a substantial impact on the choice of appropriate treatment strategy,” says Marcus Westerberg, researcher at the Department of Surgical Sciences at Uppsala University, who led the study.
In prostate cancer, the disease progression often takes decades and the risk of dying from prostate cancer therefore depends on both the characteristics of the cancer and life expectancy based on the man’s age and other diseases at the time of diagnosis. Recommendations in guidelines and care programmes are therefore also based on both cancer characteristics and life expectancy. This means that the recommended initial treatment can range from active monitoring for low-risk cancer to combinations of local and systemic treatment for high-risk cancer.
High average age at disease onset
As the average age at diagnosis of prostate cancer is often high and the cancer often progresses very slowly, it is particularly important to know the long-term risk of death from prostate cancer in order to choose the best treatment for patients. Previously, not much has been known about this.
“We wanted to fill that knowledge gap, so we looked at outcomes up to 30 years after the men were diagnosed. In all cases, we had information about the characteristics of the cancer, treatment and the patient’s life expectancy based on age and comorbidity,” says Westerberg.
The researchers used data from the Prostate Cancer Database Sweden (PCBase), which contains information from the National Prostate Cancer Register (NPCR) and other health data registers. They focused on men who had received the recommended treatment for prostate cancer that had not spread in the body. Using statistical modelling, the researchers estimated the lifetime risk of dying from prostate cancer and other causes.
11 per cent risk of dying of cancer
For men with low-risk cancer and short life expectancy (less than 10 years), the risk of dying from prostate cancer was 11% and the risk of dying from other causes was 89% within 30 years of diagnosis.
For men with high-risk cancer (eg stage T3, PSA 30ng/mL and Gleason score 8) and long life expectancy (over 15 years), the risk of dying from prostate cancer was 34% and the risk of dying from other causes was 55% within 30 years of diagnosis.
“We hope that our results will be used to provide a realistic picture of the prognosis for men with prostate cancer. Our study shows that most men who receive the recommended treatment have a good prognosis,” Westerberg concludes.
Life expectancy was based on age and comorbidity. Examples of low-risk cancers are stage T1, PSA 5ng/mL and Gleason score 6. Examples of high-risk cancers are stage T3, PSA 30ng/mL and Gleason score 8.
Scientists at The Wistar Institute have discovered that a class of FDA-approved cancer drugs known as PARP1 inhibitors can effectively combat Epstein-Barr virus (EBV)-driven lymphomas. The findings, published in the Journal of Medical Virology, demonstrate that these drugs, which work by blocking the activity of the PARP1 enzyme, can halt tumour growth by interfering with the EBV’s ability to activate key cancer-promoting genes.
“We’ve uncovered a completely different mechanism for how PARP inhibitors work in EBV-positive cancers,” said Italo Tempera, PhD, associate professor at Wistar’s Ellen and Ronald Caplan Cancer Center and senior author of the study. “Instead of preventing DNA damage from repairing itself in the tumours, like these drugs do in other cancers, they essentially cut off the virus’s ability to hijack cellular machinery to drive cancer growth. This opens up exciting possibilities for repurposing existing FDA-approved drugs to treat EBV-associated cancers.”
EBV infects over 90% of the global population. While most people with the virus remain symptom-free, immunocompromised individuals such as people with HIV and transplant recipients have an increased risk of EBV causing several types of cancer, including various lymphomas and carcinomas. Despite the virus’s clear role in driving these malignancies, no specific therapies currently target EBV-driven cancer.
In search of such a therapy, Tempera and his research team focused on PARP1, a cellular protein that is known primarily for its role in DNA repair. In cancer treatment, PARP inhibitors typically work by preventing cancer cells from repairing their DNA, causing them to die. However, Tempera’s team had previously discovered that PARP1 plays a very different role in EBV infection: It helps control which genes are accessible and active, essentially acting as a master regulator of gene expression.
“Think of PARP1 as a key that opens up DNA to make certain genes readable,” explained Tempera. “EBV uses this key to unlock cancer-promoting genes. When we block PARP1, we’re essentially taking away the key so the virus can’t get in and use our DNA for its own purposes.”
Using a mouse model of EBV-driven lymphoma, the researchers treated the animals with BMN 673 (talazoparib/talzenna), a PARP inhibitor that has already been approved for breast cancer treatment. Compared to controls, the treated mice showed an 80% reduction in tumour growth, and the cancer’s ability to spread to other organs was significantly reduced. Further, when the team analysed the tumours, they found no increase in DNA damage in the treated animals – the hallmark of how PARP inhibitors typically work. Instead, they discovered that PARP1 inhibition disrupted a critical partnership between the viral protein EBNA2 and the cellular oncogene MYC.
“EBNA2 is like the conductor of an orchestra, directing cellular genes to play a cancer symphony,” said Tempera. “It specifically turns on MYC, which is one of the most important cancer-promoting genes. When we inhibit PARP1, EBNA2 can’t effectively activate MYC anymore, and the whole cancer program falls apart.”
The findings have significant therapeutic implications. Because PARP inhibitors are already FDA-approved and their safety profiles are well established, the path to clinical application could be accelerated compared to developing entirely new drugs.
The research also suggests this approach might work beyond EBV-associated lymphomas. The team is now investigating whether PARP inhibitors could be effective against other EBV-driven cancers, including nasopharyngeal and gastric carcinomas. Additionally, given EBV’s suspected role in autoimmune diseases, the researchers are exploring whether PARP1’s regulation of viral gene expression might contribute to these conditions.
“This work really showcases the power of understanding fundamental viral biology,” said Tempera. “We’re taking insights from basic virology research and translating them into potential therapies. With further development, this approach could provide new hope for patients with EBV-associated cancers who currently have limited treatment options.”
Pretoria, 15 July 2025 – The South African Health Products Regulatory Authority (SAHPRA) was notified of the Lancet Global Health 2025; 13: e1250, an investigational study and its findings on substandard anti-cancer medications in Sub-Saharan African countries, including Ethiopia, Kenya, Malawi, and Cameroon. This study did not include South Africa. The seven (7) medicines/dosage forms mentioned in the study are cisplatin, oxaliplatin, methotrexate, doxorubicin, cyclophosphamide, ifosfamide, and leucovorin. The specific brands mentioned/shown in the article are neither registered nor marketed in South Africa.
SAHPRA, in terms of the Medicines and Related Substances Act 101 of 1965, as amended, and its General Regulations, requires medicines marketed in the country to meet prescribed requirements and adhere to set standards. Every batch of medicine produced must undergo testing to ensure that the integrity of the product is consistent with approved specifications before the release for sale, and imported medicines must additionally comply with the Guideline for Post-Importation Testing.
SAHPRA commenced internal processes to verify whether any of the South African-registered cancer medicines with the mentioned Active Pharmaceutical Ingredients (API) might have been affected or implicated. The cancer products registered and marketed in South Africa were not implicated/affected by the investigational study and its findings on substandard anti-cancer medicines. SAHPRA conducts risk-based post-market surveillance (PMS), sampling, and testing on high-risk medical products.
SAHPRA is satisfied that the marketed and registered cancer medicines meet the appropriate specifications; therefore, no substandard cancer medicines were detected.
“SAHPRA is committed to the three pillars of quality, safety, and efficacy. I am satisfied that our rigorous regulatory processes have borne fruit and that all patients, especially cancer patients, can rest assured that their health and well-being are not compromised,” indicated SAHPRA CEO, Dr Boitumelo Semete-Makokotlela.
Serious quality defects were found in a significant number of cancer medications from sub-Saharan Africa, according to new research from the University of Notre Dame.
For the study published in The Lancet Global Health, researchers collected different cancer medications from Cameroon, Ethiopia, Kenya and Malawi and evaluated whether each drug met regulatory standards. Researchers considered a variety of factors, including appearance, packaging, labelling and, most importantly, the assay value.
The assay value is the quantity of active pharmaceutical ingredient (API) found in each drug. To meet safety standards, most products should be within a range of 90 to 110% of the right amount of API. Researchers measured the API content of each product and compared that number to what was designated on the medication packaging.
“It is important that cancer medications contain the right amount of the active ingredients so the patient gets the correct dose,” said Marya Lieberman, professor of chemistry and biochemistry at Notre Dame and lead author of the study. “If the patient’s dose is too small, the cancer can survive and spread to other locations. If the patient’s dose is too high, they can be harmed by toxic side effects from the medicine.”
One in six cancer medications tested was found to contain the incorrect quantity of API, with tested medications having APIs ranging from 28 to 120%. The study evaluated 251 samples of cancer medications collected from major hospitals and private markets in all four countries.
The study, funded by the National Cancer Institute of the National Institutes of Health, is among the first to evaluate cancer drug quality in sub-Saharan Africa. Currently, sub-Saharan Africa has no pharmaceutical regulatory laboratories carrying out chemical analyses for cancer drugs according to the standards required for regulatory purposes.
Yet, the need for cancer drugs is growing.
“We found bad-quality cancer medications in all of the countries, in all of the hospital pharmacies and in the private markets,” said Lieberman, an affiliate of Notre Dame’s Eck Institute for Global Health and Harper Cancer Research Institute. “We learned that visual inspection, which is the main method for detecting bad-quality cancer drugs in sub-Saharan Africa today, only found one in 10 of the bad products.”
In their study, the researchers explained how a combination of high demand for cancer medications, lack of regulatory capacity, and poor manufacturing, distribution and storage practices likely created a problematic environment throughout sub-Saharan Africa. They also argue that given these factors and the global supply chain for pharmaceuticals, substandard cancer medications are likely present in other low and middle-income countries as well.
Lieberman and her team identified several strategies that could help the global community address poor-quality cancer medications:
Provide inexpensive technologies at the point of care to screen for bad-quality cancer medicines and create policies for how to respond to products that fail screening tests.
Help regulatory agencies in low and middle-income countries get safety equipment and training so they can analyze the quality of cancer medicines in their markets, conduct root-cause investigations when products fail testing, take quick regulatory actions enabled by lab data and share data about bad-quality products.
Perform cost-benefit analyses of interventions that tackle common problems (such as medications being out of stock, unsafe shipping, storage or dispensing practices, and lack of availability or affordability of medications) to help policymakers and funders get the most impact on patient outcomes from their available resources.
Work with care providers to develop site-specific response policies and messaging for patients and engage regulators, donors and other resources.
Lieberman and her lab are developing a user-friendly technology called the chemoPAD for screening cancer medications. This low-cost paper device could potentially help hospitals, pharmacies and health care professionals in low and middle-income countries monitor drug quality without restricting a patient’s access to the medication.
“This is all part of a bigger project aimed at developing the ChemoPAD as a point-of-care testing device that we can use, something that’s more accurate in detecting poor-quality products than just visual inspection,” Lieberman said.
“There are lots of medicines where the regulators don’t have enough resources to verify the quality, and some manufacturers take advantage of that to cut corners. There are also problems with distribution systems, so even if a product is good quality when it leaves the manufacturer, it may be degraded during shipping or storage. These products flow into low and middle-income countries, and they get used on patients. I want to change that.”
A cancer patient receiving care at a public health facility in Gauteng. (Photo: Rosetta Msimango/Spotlight)
By Chris Bateman
Experts say cancer patients in the public sector in South Africa are dying for avoidable reasons like dysfunctional referral systems and a lack of medical imaging and treatment. We look at efforts to get the country’s battle with cancer back on track.
Many people with cancer in Gauteng have not been able to access the treatment and care they require in recent years. Though activists and the provincial government are at odds about what should, or should have been, done about it, nobody is denying that there is a problem.
At the same time, there have also been issues at a national level, with South Africa’s key cancer strategy having lapsed. The National Cancer Strategic Framework for South Africa 2017 – 2022 was previously extended to also cover 2023. Medical Brief recently reported that a new strategy is on the verge of being signed by the Director-General of Health.
The committee meant to advise the minister on cancer has also lapsed. Dr Busisiwe Ndlovu, the top government official in charge of non-communicable diseases (NCDs), said that the term of the Ministerial Advisory Committee on Cancer expired in early 2024, and new members were pending the approval of Health Minister Dr Aaron Motsoaledi. She was speaking at the KwaZulu-Natal leg of a cancer research and innovation strategy workshop in May. These consultative meetings are taking place across the country’s provinces. It aims to shape a national research and innovation strategy based on the World Health Organization’s cancer control pillars: prevention, early detection and diagnosis, treatment, and palliative care and survivorship.
The scale of the problem
While researchers anticipate that rates of infectious diseases like HIV and tuberculosis in South Africa will decline in the coming decade or two, rates of NCDs, including diabetes and cancers, are expected to increase. According to the WHO, an estimated one in five people will develop some form of cancer in their lifetimes. Increases in developing countries are expected to be particularly steep.
According to a StatsSA report published in 2023, and based on National Cancer registry (NCR) numbers and StatsSA’s mortality data, cancer-related deaths in the country increased by 29% from 2008 to 2018. They reported that 85 000 people were diagnosed with cancer in 2019 and that 44 000 died of cancers in 2018. Experts previously told Spotlight that the estimate of cancer cases may be an undercount of as much as 40%.
The most common cancers in men were prostate, colorectal, and lung – around one in four cancer diagnoses in men were for prostate cancer. Bronchus and lung cancer accounted for just under 19% of cancer-related deaths in men, while prostate cancer accounted for around 17%.
Among women, the most diagnosed cancers were breast cancer at around 23% of diagnoses and cervical cancer at around 16% of diagnoses. Cervical cancer accounted for just under 18% of all cancer deaths in women and breast cancer for 17%.
The NCR recorded 87 853 new laboratory-confirmed cancer cases in 2023, although this figure likely underestimated the true burden as it excluded clinically or radiologically diagnosed cancers, Dr Judith Mwansa-Kambafwile, senior epidemiologist with the NCR told attendees at the Durban workshop.
In a paper published in the South African Journal of Oncology in 2022, researchers calculate that cancer incidence (new cases per year) in South Africa could double from around 62 000 in 2019 to 121 000 in 2030. This is due to two factors: firstly, South Africa’s population is aging and cancers generally become more common as people age. And secondly, the risk of cancers is generally increasing for people of all ages. The researchers focused on only the five most common types of cancer, but an NCR report shows a very wide variety of cancers are being diagnosed in the country.
Since not all cancers are diagnosed, the real numbers are likely substantially higher than reported. There is also no single repository of all cancer diagnoses in the country – for the above quoted article researchers used both data from Discovery Health Medical Scheme and from the NCR.
The data gap
Cancer statistics in South Africa has been largely based on pathology results, which is to say blood or biopsies that were tested in the lab. Other types of diagnoses, such as those based on symptoms and scans have not always been counted systematically. One recent initiative aimed at addressing this data gap is a patient-led registry that feeds information into the NCR.
Mwansa-Kambafwile, explained that the NGO, Living with Cancer, was driving the patient-led registry, aimed at cross referencing and supplementing patient records with her NCR’s own patient database. Leaflets in oncologists’ reception rooms encouraged patients to upload their pathology/histology test results onto the Living with Cancer website via a standard online National Department of Health form. A national shopping mall campaign in May was aimed at boosting awareness.
“Living with Cancer had a Memorandum of Understanding with us and in addition, links cancer survivors with the same type of cancer to one another in support groups online where they can share experiences and knowledge,” she added.
Dr Mazvita Muchengeti, who heads up work on the NCR at the National Health Laboratory Services which is part of the National Institute for Communicable Diseases (NICD), previously told Spotlight that cancer was made a reportable disease under the National Health Act in 2011. While compulsory reporting has improved data on cancer cases, she added: “There is an increase in the number of reported cancers; this does not necessarily translate to an increase in cancer, we are just counting cancer cases better because reporting is now compulsory.”
Another new strategy
In light of the country’s cancer burden, a group of organisations is leading the development of a new National Cancer Research and Innovation Strategy. This collective includes the Nuclear Medicine Research Infrastructure at the University of Pretoria, the South African Medical Research Council, and the Department of Science, Technology and Innovation, in partnership with the National Department of Health.
They are hosting provincial workshops to help understand the current state of cancer research in South Africa, identify key challenges, set national priorities, and develop a strong, future-focused strategy. These workshops are part of a broader plan to make sure the strategy is inclusive, based on evidence, and meets the country’s needs.
This research and innovation strategy differs from the health department’s National Cancer Strategic Framework, which guides provinces as to what the cancer priorities are.
‘Integrated cancer care approach’
At the Durban workshop, Ndlovu, emphasised the need for an integrated cancer care approach across all levels of the healthcare system. She noted the importance of streamlined referral pathways and urgent attention to waiting times, care packages, registry improvements, and financing. The expired national cancer strategy required urgent evaluation and revision, Ndlovu added.
A clear pattern emerging from these workshops is one whereby cancers are often diagnosed too late, and patients frequently struggle to access timely, appropriate care.
Also at the Durban workshop, Professor Jeannette Parkes, Head of Radiation Oncology at Groote Schuur Hospital and the University of Cape Town, outlined the many systemic barriers to early detection. These included socio-cultural factors, urban-rural divides, and broken referral systems.
“We have a massive issue with accessing imaging services, biopsy support, pathology services, and their costs,” she said.
Parkes, who is also President of the College of Radiation Oncology of South Africa and clinical director of the Access to Care Cape Town programme, said early cancer detection was better in the private sector because patients could access and afford the necessary systems and diagnostic technology. The remaining 85% of the population depended on the public sector, in particular overburdened primary healthcare clinics but also on all levels of care.
“There’s a bias towards urban versus rural areas and too often a failure to refer. The referral pathway is problematic and differs from province to province and in various settings. We have a massive issue with regards to accessing imaging services, while biopsy support and pathology services and their costs are also a big issue,” she told the workshop.
Late diagnosis
At the Johannesburg meeting, late diagnosis was singled out as a particular problem when it comes to cervical cancer. Dr Mary Kawonga, public health specialist with the Gauteng Department of Health and Wits School of Public Health, said that 16% of women screened at Charlotte Maxeke Academic Hospital’s drainage district had pre-cancerous lesions, underlining the lack of preventative care. “Patients often only begin treatment on their sixth visit,” she said, citing the failure of diagnostic tools, referral inefficiencies, and poor implementation of available technologies.
Dr Mariza Vorster, Head of Nuclear Medicine at the University of KwaZulu-Natal and Inkosi Albert Luthuli Academic Hospital, said that insufficient specialists and excessive patient loads result in unacceptable turnaround times for diagnosis.
Clinicians often get blamed for delays, but as Dr Sheynaz Bassa, Head of Radiation Oncology at Steve Biko Academic Hospital, pointed out, many patients wait weeks or months to afford transport to care facilities. “By the time they get to us, they’re already in crisis mode,” she said. “Peripheral clinics and hospitals must improve referral systems before we can make real progress.”
Salomé Meyer, Director of Cancer Alliance, alleged that survivorship care is almost entirely absent in both the public and private sectors. “Supportive and palliative care often ends when treatment stops. Survivors are left without co-ordinated care,” she said.
Apart from improving screening and referral systems, other recommendations emerging from the workshops included better coordination between clinicians and the NCR, leveraging mobile technology like the health department’s Mom Connect app to reduce clinic visits and fast-track referrals. Greater community involvement in setting research priorities, using mobile clinics to conduct cancer screening in rural areas, and increasing awareness for breast self-examination. More research into the genetic factors relating to cancers in South Africa was also argued for.
Call for new cancer institute
Meyer has been leading a call for South Africa to establish a National Cancer Institute (NCI).
“An NCI would develop clear guidelines on treatment protocols, workforce allocation, and facility requirements,” she said. With South Africa transitioning toward a National Health Insurance system, Meyer said an NCI would help plan resource allocation based on cancer projections, enabling smarter investments in infrastructure, technology, and staffing.
The lapsed National Cancer Strategic Framework lacked province-specific detail, leaving provinces to adapt guidelines as they saw fit, often leading to fragmented service delivery, she added. Meyer said decentralisation was essential. “We can no longer restrict cancer treatment to tertiary hospitals. Many district and regional facilities could provide diagnostics and some treatments if properly resourced,” she said.
A reset of South Africa’s disease monitoring and research infrastructure has been on the cards for some time. The NICD was set to be replaced by the new National Public Health Institute of South Africa (NAPHISA) after the NAPHISA Act became law in 2020. Five years later, NAPHISA has not yet been established. On the face of it, NAPHISA would be a natural home for an entity like the proposed NCI were it to be created.
A sample of Aspergillus flavus cultured in the Gao Lab. (Credit: Bella Ciervo)
University of Pennsylvania-led researchers have turned a deadly fungus into a potent cancer-fighting compound. After isolating a new class of molecules from Aspergillus flavus, a toxic crop fungus linked to deaths in excavating ancient tombs, the researchers modified the chemicals and tested them against leukaemia cells. The result was a promising cancer-killing compound that rivals FDA-approved drugs and opens up new frontiers in the discovery of more fungal medicines.
“Fungi gave us penicillin,” says Sherry Gao, Presidential Penn Compact Associate Professor in Chemical and Biomolecular Engineering (CBE) and in Bioengineering (BE) and senior author of a new paper in Nature Chemical Biology on the findings. “These results show that many more medicines derived from natural products remain to be found.”
From Curse to Cure
A. flavus, named for its yellow spores, has long been a microbial villain. After archaeologists opened King Tutankhamun’s tomb in the 1920s, a series of untimely deaths among the excavation team fuelled rumours of a pharaoh’s curse. Decades later, doctors theorised that fungal spores, dormant for millennia, could have played a role.
In the 1970s, a dozen scientists entered the tomb of Casimir IV in Poland. Within weeks, 10 of them died. Later investigations revealed the tomb contained A. flavus, whose toxins can lead to lung infections, especially in people with compromised immune systems.
Now, that same fungus is the unlikely source of a promising new cancer therapy.
A Rare Fungal Find
The therapy in question is a class of ribosomally synthesised and post-translationally modified peptides, or RiPPs, pronounced like the “rip” in a piece of fabric. The name refers to how the compound is produced – by the ribosome, a tiny cellular structure that makes proteins – and the fact that it is modified later, in this case, to enhance its cancer-killing properties.
“Purifying these chemicals is difficult,” says Qiuyue Nie, a postdoctoral fellow in CBE and the paper’s first author. While thousands of RiPPs have been identified in bacteria, only a handful have been found in fungi. In part, this is because past researchers misidentified fungal RiPPs as non-ribosomal peptides and had little understanding of how fungi created the molecules. “The synthesis of these compounds is complicated,” adds Nie. “But that’s also what gives them this remarkable bioactivity.”
Hunting for Chemicals
To find more fungal RiPPs, the researchers first scanned a dozen strains of Aspergillus, which previous research suggested might contain more of the chemicals.
By comparing chemicals produced by these strains with known RiPP building blocks, the researchers identified A. flavus as a promising candidate for further study.
Genetic analysis pointed to a particular protein in A. flavus as a source of fungal RiPPs. When the researchers turned the genes that create that protein off, the chemical markers indicating the presence of RiPPs also disappeared.
This novel approach – combining metabolic and genetic information – not only pinpointed the source of fungal RiPPs in A. flavus, but could be used to find more fungal RiPPs in the future.
A Potent New Medicine
After purifying four different RiPPs, the researchers found the molecules shared a unique structure of interlocking rings. The researchers named these molecules, which have never been previously described, after the fungus in which they were found: asperigimycins.
Even with no modification, when mixed with human cancer cells, asperigimycins demonstrated medical potential: two of the four variants had potent effects against leukaemia cells.
Another variant, to which the researchers added a lipid found in bees’ royal jelly, performed as well as cytarabine and daunorubicin, two FDA-approved drugs that have been used for decades to treat leukaemia.
Cracking the Code of Cell Entry
To understand why lipids enhanced asperigimycins’ potency, the researchers selectively turned genes on and off in the leukaemia cells. One gene, SLC46A3, proved critical in allowing asperigimycins to enter leukaemia cells in sufficient numbers.
That gene helps materials exit lysosomes, the tiny sacs that collect foreign materials entering human cells. “This gene acts like a gateway,” says Nie. “It doesn’t just help asperigimycins get into cells, it may also enable other ‘cyclic peptides’ to do the same.”
Like asperigimycins, those chemicals have medicinal properties – nearly two dozen cyclic peptides have received clinical approval since 2000 to treat diseases as varied as cancer and lupus – but many of them need modification to enter cells in sufficient quantities.
“Knowing that lipids can affect how this gene transports chemicals into cells gives us another tool for drug development,” says Nie.
Disrupting Cell Division
Through further experimentation, the researchers found that asperigimycins likely disrupt the process of cell division. “Cancer cells divide uncontrollably,” says Gao. “These compounds block the formation of microtubules, which are essential for cell division.”
Notably, the compounds had little to no effect on breast, liver or lung cancer cells – or a range of bacteria and fungi – suggesting that asperigimycins’ disruptive effects are specific to certain types of cells, a critical feature for any future medication.
Future Directions
In addition to demonstrating the medical potential of asperigimycins, the researchers identified similar clusters of genes in other fungi, suggesting that more fungal RiPPS remain to be discovered. “Even though only a few have been found, almost all of them have strong bioactivity,” says Nie. “This is an unexplored region with tremendous potential.”
The next step is to test asperigimycins in animal models, with the hope of one day moving to human clinical trials. “Nature has given us this incredible pharmacy,” says Gao. “It’s up to us to uncover its secrets. As engineers, we’re excited to keep exploring, learning from nature and using that knowledge to design better solutions.”
Looking to nature for answers to complex questions can reveal new and unprecedented results that can even affect cells on molecular levels. For instance, human cells oxidise glucose to produce ATP (adenosine triphosphate), an energy source necessary for life.
Cancer cells produce ATP through glycolysis, which does not utilise oxygen even under conditions where oxygen is present, and convert glucose into pyruvic acid and lactic acid. This method of producing ATP, known as the Warburg effect, is considered inefficient, thus raising questions as to why cancer cells choose this energy pathway to fuel their proliferation and survival.
In search for this energy catalyst, Associate Professor Akiko Kojima-Yuasa’s team at Osaka Metropolitan University’s Graduate School of Human Life and Ecology analysed the cinnamic acid ester ethyl p-methoxycinnamate, a main component of kencur ginger, and its mechanism of action. In previous research, the team discovered that ethyl p-methoxycinnamate has inhibitory effects on cancer cells. Furthering their study, the acid ester was administered to Ehrlich ascites tumour cells to assess which component of the cancer cells’ energy pathway was being affected.
Results revealed that the acid ester inhibits ATP production by disrupting de novo fatty acid synthesis and lipid metabolism, rather than through glycolysis as commonly theorised. Further, the researchers discovered acid ester-induced inhibition triggered increased glycolysis, which acted as a possible survival mechanism in the cells. This adaptability was theorised to be attributed to ethyl p-methoxycinnamate’s inability to induce cell death.
“These findings not only provide new insights that supplement and expand the theory of the Warburg effect, which can be considered the starting point of cancer metabolism research, but are also expected to lead to the discovery of new therapeutic targets and the development of new treatment methods,” stated Professor Kojima-Yuasa.
Genetic mutations and cell maturity as key factors in acute myeloid leukaemia drug resistance
Photo by Tima Miroshnichenko on Pexels
An international study led by the University of Colorado Cancer Center has uncovered why a widely used treatment for acute myeloid leukaemia (AML) doesn’t work for everyone. The findings could help doctors better match patients with the therapies most likely to work for them.
Researchers analysed data from 678 AML patients, the largest group studied to date for this treatment, and found that both gene mutations and the maturity of leukaemia cells affect how patients respond to a drug combination of venetoclax and hypomethylating agents (HMA).
“Venetoclax-based therapies are now the most common treatment for newly diagnosed AML,” said Daniel Pollyea, MD, MS, professor of medicine at University of Colorado. “But not all patients respond the same way. Our goal was to figure out why and give doctors better tools to predict outcomes at the start.”
Mutations and maturity of leukaemia cells
AML is a fast-growing cancer of the blood and bone marrow, most often seen in older adults. Many patients can’t tolerate traditional chemotherapy, so doctors treat them with venetoclax plus HMA. This combination has improved survival for many, but some patients still relapse or don’t respond.
The study found that patients with a certain type of AML, called “monocytic,” had worse outcomes especially if they did not have a helpful gene mutation known as NPM1. These patients were also more likely to carry other mutations, such as KRAS, that are linked to drug resistance.
“Patients with monocytic AML and no NPM1 mutation were nearly twice as likely to die from the disease,” said Pollyea. “So, it’s not just about the gene mutations. It’s also about how developed or mature the cancer cells are when treatment begins.”
Previous research often focused only on either genetic mutations or cell type. Pollyea’s team looked at both, giving them a clearer understanding of how these two factors work together to influence treatment response.
Designing therapies that shut down cancer cell escape routes
“We learned that some cancer cells basically find a back door to evade the treatment,” said Pollyea. “By identifying how and why that happens, we can begin designing therapies that shut down those escape routes.”
This is a powerful new way to classify AML patients by risk, enabling doctors to better predict who is likely to respond to venetoclax and who might need another approach.
“This is a major step toward personalised medicine in AML,” said Pollyea. “We’re moving closer to a world where we can look at a patient’s leukaemia on day one and know which therapy gives them the best chance and ultimately improve survival rates.”
Pollyea and his team are working to expand the study with even more patient data and hope to design a clinical trial that uses this model to guide treatment decisions.
Selective serotonin reuptake inhibitors (SSRIs) could help the immune system fight cancer, according to recent UCLA research. The study, published in Cell, found that SSRIs significantly enhanced the ability of T cells to fight cancer and suppressed tumour growth across a range of cancer types in both mouse and human tumour models.
“It turns out SSRIs don’t just make our brains happier; they also make our T cells happier – even while they’re fighting tumours,” said Lili Yang, PhD, senior author of the new study. “These drugs have been widely and safely used to treat depression for decades, so repurposing them for cancer would be a lot easier than developing an entirely new therapy.”
According to the CDC, one out of eight adults in the US takes an antidepressant, and SSRIs are the most commonly prescribed. These drugs increase levels of serotonin the brain’s “happiness hormone” by blocking the activity of a protein called serotonin transporter, or SERT.
While serotonin is best known for the role it plays in the brain, it’s also a critical player in processes that occur throughout the body, including digestion, metabolism and immune activity.
Dr Yang and her team first began investigating serotonin’s role in fighting cancer after noticing that immune cells isolated from tumours had higher levels of serotonin-regulating molecules. At first, they focused on MAO-A, an enzyme that breaks down serotonin and other neurotransmitters, including norepinephrine and dopamine.
In 2021, they reported that T cells produce MAO-A when they recognise tumours, which makes it harder for them to fight cancer. They found that treating mice with melanoma and colon cancer using MAO inhibitors, also called MAOIs – the first class of antidepressant drugs to be invented – helped T cells attack tumours more effectively.
However, because MAOIs have safety concerns, including serious side effects and interactions with certain foods and medications, the team turned its attention to a different serotonin-regulating molecule: SERT.
“Unlike MAO-A, which breaks down multiple neurotransmitters, SERT has one job – to transport serotonin,” explained Bo Li, PhD, first author of the study and a senior research scientist in the Yang lab. “SERT made for an especially attractive target because the drugs that act on it – SSRIs – are widely used with minimal side effects.”
The researchers tested SSRIs in mouse and human tumour models representing melanoma, breast, prostate, colon and bladder cancer. They found that SSRI treatment reduced average tumour size by over 50% and made the cancer-fighting T cells, known as killer T cells, more effective at killing cancer cells.
“SSRIs made the killer T cells happier in the otherwise oppressive tumour environment by increasing their access to serotonin signals, reinvigorating them to fight and kill cancer cells,” said Dr Yang, who is also a professor of microbiology, immunology and molecular genetics and a member of the UCLA Health Jonsson Comprehensive Cancer Center.
How SSRIs could boost the effectiveness of cancer therapies
The team also investigated whether combining SSRIs with existing cancer therapies could improve treatment outcomes. They tested a combination of an SSRI and anti-PD-1 antibody – a common immune checkpoint blockade (ICB) therapy – in mouse models of melanoma and colon cancer. ICB therapies block immune checkpoint molecules that normally suppress immune cell activity, allowing T cells to attack tumours more effectively.
The results were striking: the combination significantly reduced tumour size in all treated mice and even achieved complete remission in some cases.
“Immune checkpoint blockades are effective in fewer than 25% of patients,” said James Elsten-Brown, a graduate student in the Yang lab and co-author of the study. “If a safe, widely available drug like an SSRI could make these therapies more effective, it would be hugely impactful.”
To confirm these findings, the team will investigate whether real-world cancer patients taking SSRIs have better outcomes, especially those receiving ICB therapies. About 20% of cancer patients are already taking the medication, Dr Yang said.
Dr Yang added that using existing FDA-approved drugs could speed up the process of bringing new cancer treatments to patients, making this research especially promising.
“Studies estimate the bench-to-bedside pipeline for new cancer therapies costs an average of $1.5 billion,” she said. “When you compare this to the estimated $300 million cost to repurpose FDA-approved drugs, it’s clear why this approach has so much potential.”
