Category: Cancer

South African Study Identifies Two New Breast Cancer Genes in Black Women

Genetic factors contribute to some 30% of breast cancer cases in SA, necessitating investment in genomic research in African contexts.

Photo by National Cancer Institute

A seminal genetic study published in Nature Communications has discovered two genetic variants linked to breast cancer in black South African women, deepening knowledge about the genetic basis for this disease in African populations.

The genome-wide association study (GWAS) of breast cancer is the first to have been done in African women living on the continent.

A GWAS is a powerful research method that scans the entire DNA of many people to find genetic differences associated with a specific disease or trait.

In this case, the scientists at the Sydney Brenner Institute for Molecular Bioscience (SBIMB) scanned for breast cancer and found consistent genetic patterns in black South African women.

The SBIMB researchers discovered genetic signals around the gene RAB27A, a member of the RAS oncogene family, and USP22, a gene which is highly active in breast cancer cells and associated with a poor health prognosis.

“These genes have not been associated with the disease before, which is an important advance in understanding breast cancer risk and biology in women of African ancestry,” says Dr Mahtaab Hayat, the lead author of the study.

The two new genetic variants were identified in black South African women with breast cancer enrolled in the Johannesburg Cancer Study, compared to women without cancer in the Africa Wits-INDEPTH Partnership for Genomic Research (AWI-Gen) study.

Until now, most breast cancer genetics research has focused on European and Asian populations, with studies of African ancestry limited primarily to African- American women, who largely descend from West African populations.

A tool that estimates lifetime cancer risk based on DNA, the polygenic risk score (PRS), performed poorly in distinguishing South African women with breast cancer from those without.

“This is because most PRSs were developed in European populations, and their inaccuracy in African populations highlights the urgent need for ancestry-specific tools in cancer risk prediction,” says Dr Jean-Tristan Brandenburg, also in the SBIMB and a lead author.

Breast cancer is the second most common cancer in South Africa and the most common cancer in women globally, with genetic factors contributing to about 30% of cases. “Our study makes a compelling case for investing in genomic research rooted in African contexts,” notes Hayat.

The potential for precision medicine

If further studies confirm these findings, the USP22 and RAB27A genes could be specific targets for new drugs. “We could potentially target harmful cancer cells while sparing healthy tissue, which is ideally what we want when administering cancer treatment,” says Distinguished Professor at the SBIMB, Chris Mathew, and a lead project investigator.

Furthermore, if a specific gene is associated with poorer survival, it can be used as a biomarker to identify more aggressive cancers and help predict which patients may need more intensive treatment and monitoring.

Understanding the genetic architecture of complex diseases helps scientists figure out the biological processes leading to these conditions and find drug targets and treatments for groups of individuals with similar disease risk profiles.

Genomic diversity in Africa is unparalleled

African populations have more genetic variation than any other population in the world, but they have been significantly underrepresented in genomic research. This means that the global understanding of disease risk, and the tools and treatment developed from it, is limited.

“The study reveals that more people can benefit from genetic discoveries. It proves that new risk factors are still out there, waiting to be found,” says Hayat.

Source: University of the Witwatersrand

A Downside of Taurine: It Drives Leukaemia Growth

SAG Leukaemia. Credit: Scientific Animations CC0

A new scientific study identified taurine, which is made naturally in the body and consumed through some foods, as a key regulator of myeloid cancers such as leukaemia, according to a paper published in the journal Nature.

The preclinical research shows that scientists are a step closer to finding new ways to target leukaemia, which is one of the most aggressive blood cancers. The Wilmot Cancer Institute investigators at the University of Rochester were able to block the growth of leukaemia in mouse models and in human leukaemia cell samples by using genetic tools to prevent taurine from entering cancer cells.

Led by Jeevisha Bajaj, PhD, the research team discovered that taurine is produced by a subset of normal cells in the bone marrow microenvironment, the tissue inside bones where myeloid cancers begin and expand. Leukaemia cells are unable to make taurine themselves, so they rely on a taurine transporter (encoded by the SLC6A6 gene) to grab taurine from the bone marrow environment and deliver it to the cancer cells.

The discovery occurred as scientists were mapping what happens within the bone marrow and its ecosystem—a longtime focus among Wilmot researchers, who have advanced the science around the microenvironment with the goal of improving blood cancer treatments.

“We are very excited about these studies because they demonstrate that targeting uptake by myeloid leukaemia cells may be a possible new avenue for treatment of these aggressive diseases,” said Bajaj, an assistant professor in the Department of Biomedical Genetics and a member of Wilmot’s Cancer Microenvironment research program.

Researchers also discovered that as leukaemia cells drink up taurine, it promotes glycolysis (a breakdown of glucose to produce energy) to feed cancer growth. Prior to this, the authors said, it was not known that taurine might have a cancer-promoting role.

Leukaemia has several subtypes and survival rates vary. This study finds that taurine transporter expression is essential for the growth of multiple subtypes including acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML), and myelodysplastic syndromes (MDS), which all originate from blood stem cells in the bone marrow. Future studies will investigate signals from the microenvironment that promote the transition of MDS, a precursor to leukaemia, to acute leukaemia.

Source: University of Rochester Medical Center

CAR-T Cell Therapy Causes ‘Brain Fog,’ Study Shows

Killer T cells about to destroy a cancer cell. Credit: NIH

After treatment with CAR-T cells, immune cells engineered to attack cancer, patients sometimes tell their doctors they feel like they have “brain fog,” or forgetfulness and difficulty concentrating.

A new Stanford Medicine-led study shows that CAR-T cell therapy causes mild cognitive impairments, independent of other cancer treatments, and that this happens via the same cellular mechanism as cognitive impairment from two other causes: chemotherapy and respiratory infections such as flu and COVID-19. The study, conducted mostly in mice, which was published in Cell, also identifies strategies for reversing the problem.

Medications that ameliorate brain fog will enable better recovery from cancer immunotherapies, the researchers said.

“CAR-T cell therapy is enormously promising,” said senior author, Michelle Monje, MD, PhD, professor in paediatric neuro-oncology. “We need to understand all its possible long-term effects, including this newly recognised syndrome of immunotherapy-related cognitive impairment, so we can develop therapeutic approaches to fix it.”

The study’s lead authors are Anna Geraghty, PhD, senior staff scientist in the Monje lab, and MD/PhD student Lehi Acosta-Alvarez.

Cognitive impairment after CAR-T cell therapy is typically mild; patients are not developing dementia, for instance. But it is frustrating and may not resolve on its own, Monje said. In mice, her team reversed the impairment using compounds similar to existing medications or medications in clinical development – meaning a treatment could be available relatively quickly, she said.

“We’re deeply interested in how cancer therapies affect cognition because it affects patients’ quality of life,” Monje said. “And this is especially important for kids because their brains are still developing.”

Investigating brain fog

CAR-T cell therapy was approved in the US for acute lymphoblastic leukaemia in 2017. The treatment involves removing some of the patient’s own immune cells, known as T cells, and engineering them to attack targets on cancer cells. The modified T cells are returned to the patient’s body, where they recognise and destroy cancer.

In addition to leukaemia, CAR-T cells are now used to treat other blood cancers, including multiple myeloma and some kinds of lymphoma, and they are being tested in clinical trials for various solid tumours. Monje and her colleagues have an ongoing trial of CAR-T cells for deadly brain stem and spinal cord tumours in children, which is beginning to show success.

Although patients report brain fog after CAR-T cell therapy, studies to measure how much cognitive impairment the therapy causes are only just emerging.

The research team wanted to get a comprehensive understanding of the situations in which CAR-T cell therapy might cause cognitive impairment. They studied mice that had tumours induced in the brain, blood, skin and bone. The researchers wanted to understand the influence on cognition of CAR-T cell treatment in combination with the tumours’ location (originating in, spreading to or staying outside the brain), as well as the degree to which the engineered cells evoked additional, accompanying immune responses. Before and after CAR-T cell treatment, the researchers used standard cognitive tests on the mice, measuring how mice responded to a novel object and navigated a simple maze.

CAR-T therapy caused mild cognitive impairment in mice with cancers originating in, metastasizing to and located completely outside the brain. The only mice tested that did not develop cognitive impairment after CAR-T treatment were those that had bone cancer that causes minimal additional inflammation beyond the cancer-fighting activity of the CAR-T cells.

“This is the first study to demonstrate that immunotherapy on its own is sufficient to cause lasting cognitive symptoms,” Monje said. “It’s also the first paper to uncover the mechanisms. We found the exact same pathophysiology we’ve seen in brain fog syndromes that occur after chemotherapy, radiation, and mild respiratory COVID-19 or influenza.”

The researchers demonstrated that the brain’s immune cells, called microglia, are key players in the problem. First, the microglia become activated by the body’s immune response. The activated, “annoyed” microglia produce inflammatory immune molecules known as cytokines and chemokines, which in turn have widespread effects throughout the brain. They are particularly harmful for oligodendrocytes, the brain cells responsible for making myelin, the fatty substance that insulates nerve fibres and helps nerves transmit signals more efficiently. Reduction in the nerves’ insulation translates into cognitive impairment.

Examining tissue samples

The scientists also analysed samples of brain tissue from human subjects who participated in the team’s ongoing clinical trial of CAR-T cells for spinal cord and brain stem tumours. Using post-mortem tissue samples, the researchers confirmed that microglia and oligodendrocytes appear dysregulated in the same way the team had observed in mice after CAR-T therapy.

In mice, the research team tested strategies to resolve the cognitive problems. They gave a compound that depleted microglia in the brains of the mice for a two-week period. After that transient depletion, the microglia  returned in the brain in a normal, non-reactive state. The mice were no longer cognitively impaired.

The researchers also gave the mice a medication that enters the brain and interferes with signals from damaging chemokines, blocking a specific receptor for these molecules.

“That alone rescued cognition,” Monje said, adding that the researchers are now exploring how to safely translate the two strategies – transiently depleting microglia or interrupting chemokine signals – in people who have had CAR-T cell therapy.

“This research further illustrates that there is a unifying principle underpinning brain fog syndromes,” said Monje, a member of the Stanford Cancer Institute. “And this particular study is so exciting because not only have we identified the cells central to this pathophysiology, we’ve found a molecular target we can investigate to treat it.”

Source: Stanford Medicine

Abdominal Ascites Fuels Immune Failure in Ovarian Cancer

Human NK cells have large nuclei stained in blue and droplets of fat stores stained in red. Image: Dr Karen Slattery, Trinity College Dublin.

New research led by Irish scientists has uncovered how lipid-rich fluid in the abdomen, known as ascites, plays a central role in weakening the body’s immune response in advanced ovarian cancer. The findings offer new insights into immune suppression in ovarian cancer and open promising avenues for future immunotherapy approaches

Over 70% of patients with ovarian cancer are diagnosed at an advanced stage, often presenting with large volumes of ascites. This ascites fluid not only supports the spread of cancer throughout the abdominal cavity but also significantly impairs the body’s immune defences.

Understanding how ascites affects the immune system is important for developing better treatments that use the immune system to fight cancer. 

In this recent study, researchers from Trinity and University College Dublin explored how ascites disrupts immune cell function, with a particular focus on natural killer (NK) cells and T cells, which are key players in the body’s ability to eliminate tumours.

By analysing the contents of ascites fluid from ovarian cancer patients, the team identified a group of fat molecules called phospholipids as key drivers of this immune dysfunction. 

Dr Karen Slattery, Research Fellow in the Trinity Translational Medicine Institute, is the first author of the research article just published in the leading international journal Science Immunology.

She said: “We found that these lipids interfere with NK cell metabolism and suppress their ability to kill cancer cells. Crucially, we also discovered that blocking the uptake of these phospholipids into NK cells using a specific receptor blocker can restore their anti-tumour activity, which offers a compelling new target for therapeutic intervention.” 

“This work adds a critical piece to the puzzle of why ovarian cancer is so aggressive and has such poor outcomes. While the immune system is naturally equipped to detect and destroy cancer cells, this function is switched off in many individuals with ovarian cancer, and we now know that this is in part due to the fat-rich environment created by ascites.” 

Prof Lydia Lynch, formerly based in Trinity and now in Princeton University, is the senior author of the research article. She said: “This study marks a significant advancement in ovarian cancer research, identifying a new mechanism underpinning immune failure and laying the foundation for new therapies that could restore immune function in these patients. By targeting the fat-induced suppression of immune cells, future treatments could empower the body’s own immune defences to fight back and in doing so, improve outcomes for ovarian cancer patients.”

Source: Trinity College Dublin

Removing Ovaries and Fallopian Tubes Linked to Lower Risk of Early Death Among Certain Breast Cancer Patients

Photo by National Cancer Institute on Unsplash

Women diagnosed with breast cancer who carry particular BRCA1 and BRCA2 genetic variants are offered surgery to remove the ovaries and fallopian tubes as this dramatically reduces their risk of ovarian cancer. Now, Cambridge researchers have shown that this procedure – known as bilateral salpingo-oophorectomy (BSO) – is associated with a substantial reduction in the risk of early death among these women, without any serious side-effects.

Women with certain variants of the genes BRCA1 and BRCA2 have a high risk of developing ovarian and breast cancer. These women are recommended to have their ovaries and fallopian tubes removed at a relatively early age – between the ages 35 and 40 years for BRCA1 carriers, and between the ages 40 and 45 for BRCA2 carriers.

Previously, BSO has been shown to lead to an 80% reduction in the risk of developing ovarian cancer among these women, but there is concern that there may be unintended consequences as a result of the body’s main source of oestrogen being removed, which brings on early menopause. This can be especially challenging for BRCA1 and BRCA2 carriers with a history of breast cancer, as they may not typically receive hormone replacement therapy to manage symptoms. The overall impact of BSO in BRCA1 and BRCA2 carriers with a prior history of breast cancer remains uncertain. 

Ordinarily, researchers would assess the benefits and risks associated with BSO through randomised controlled trials, the ‘gold standard’ for testing how well treatments work. However, to do so in women who carry the BRCA1 and BRCA2 variants would be unethical as it would put them at substantially greater risk of developing ovarian cancer.

To work around this problem, a team at the University of Cambridge, in collaboration with the National Disease Registration Service (NDRS) in NHS England, turned to electronic health records and data from NHS genetic testing laboratories collected and curated by NDRS to examine the long-term outcomes of BSO among BRCA1 and BRCA2 PV carriers diagnosed with breast cancer. The results of their study, the first large-scale study of its kind, are published today in The Lancet Oncology.

The team identified a total of 3400 women carrying one of the BRCA1 and BRCA2 cancer-causing variants (around 1700 women for each variant). Around 850 of the BRCA1 carriers and 1,000 of the BRCA2 carriers had undergone BSO surgery.

Women who underwent BSO were around half as likely to die from cancer or any other cause over the follow-up period (a median follow-up time of 5.5 years). This reduction was more pronounced in BRCA2 carriers compared to BRCA1 carriers (a 56% reduction compared to 38% respectively). These women were also at around a 40% lower risk of developing a second cancer.

Although the team say it is impossible to say with 100% certainty that BSO causes this reduction in risk, they argue that the evidence points strongly towards this conclusion.

Importantly, the researchers found no link between BSO and increased risk of other long-term outcomes such as heart disease and stroke, or with depression. This is in contrast to previous studies that found evidence in the general population of an association between BSO and increased risk of these conditions.

First author Hend Hassan, a PhD student at the Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, and Wolfson College, Cambridge, said: “We know that removing the ovaries and fallopian tubes dramatically reduces the risk of ovarian cancer, but there’s been a question mark over the potential unintended consequences that might arise from the sudden onset of menopause that this causes.

“Reassuringly, our research has shown that for women with a personal history of breast cancer, this procedure brings clear benefits in terms of survival and a lower risk of other cancers without the adverse side effects such as heart conditions or depression.”

Most women undergoing BSO were white. Black and Asian women were around half as likely to have BSO compared to white women. Women who lived in less deprived areas were more likely to have BSO compared to those in the most-deprived category.

Hassan added: “Given the clear benefits that this procedure provides for at-risk women, it’s concerning that some groups of women are less likely to undergo it. We need to understand why this is and encourage uptake among these women.”

Professor Antonis Antoniou, from the Department of Public Health and Primary Care, the study’s senior author, said: “Our findings will be crucial for counselling women with cancer linked to one of the BRCA1 and BRCA2 variants, allowing them to make informed decisions about whether or not to opt for this operation.”

Professor Antoniou, who is also Director of the Cancer Data-Driven Detection programme, added: “The study also highlights the power of exceptional NHS datasets in driving impactful, clinically relevant research.”

The research was funded by Cancer Research UK, with additional support from the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre.

The University of Cambridge is fundraising for a new hospital that will transform how we diagnose and treat cancer. Cambridge Cancer Research Hospital, a partnership with Cambridge University Hospitals NHS Foundation Trust, will treat patients across the East of England, but the research that takes place there promises to change the lives of cancer patients across the UK and beyond. Find out more here.

Reference

Hassan, H et al. Long-term health outcomes of bilateral salpingo-oophorectomy in BRCA1 and BRCA2 pathogenic variant carriers with personal history of breast cancer: a retrospective cohort study using linked electronic health records. Lancet Oncology; 7 May 2025; DOI: 10.1016/S1470-2045(25)00156-1

The original text of this story is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

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Does Cancer Treatment Affect Connections in the Brain?

Photo by Fakurian Design on Unsplash

New research published in the Journal of Magnetic Resonance Imaging has uncovered changes in brain connectivity during chemotherapy in patients with breast cancer.

In the study of 55 patients with breast cancer and 38 controls without cancer, investigators conducted functional magnetic resonance imaging scans of participants’ brains over several months.

Scans from patients revealed changes in brain connectivity, particularly in the frontal-limbic system (involved in executive functions) and the cerebellar cortex (linked to memory) throughout the course of treatment. These changes got worse and spread more as chemotherapy continued.

“The findings suggest that chemotherapy can quickly disrupt brain function in breast cancer patients, potentially contributing to cognitive issues,” the authors wrote.

Source: Wiley

Hyperbaric Oxygen for Radiation-induced Injuries Provides Lasting Relief

Photo by National Cancer Institute on Unsplash

Hyperbaric oxygen treatment provides long-term relief for patients suffering from late radiation-induced injuries after treatment of cancer in the lower abdominal area. Five years after hyperbaric oxygen therapy, the positive effects remain. This has been shown in a study conducted at the University of Gothenburg, published in eClinicalMedicine.

Radiation therapy is a component of many cancer treatments in organs such as the prostate, colon, ovaries and cervix. While tumour cells are destroyed, 5-10% of patients experience severe side effects due to healthy tissue being affected by the radiation therapy.

Symptoms may include urinary incontinence, bleeding and severe pain from the lower abdomen that becomes both physically and socially disabling. These problems can occur several years after radiation therapy and cause chronic and increasing discomfort.

Researchers have previously shown that patients experience significantly less discomfort after hyperbaric oxygen treatment. The question in the current study was whether the relief would last over several years. The time aspect is important for future decisions on broader use of the method.

From severe problems to a normal life 

Initially, all participants had severe symptoms. The group that was randomly assigned to hyperbaric oxygen treatment fared significantly better than the control group in terms of incontinence, bleeding and pain. The positive effects were sustained over the five year follow-up period. 

Nicklas Oscarsson, senior consultant in anaesthesiology and intensive care, and researcher at the University of Gothenburg and Sahlgrenska University Hospital was the principle investigator of the study:

“Patients who respond to treatment go from being very distressed by their symptoms and restricted by their need to have quick access to a toilet, to being able to live a fully normal life. Now we know that this pronounced improvement last for at least five years. The treatment can therefore lead to the healing of an otherwise chronic injury,” he states.

The effects achieved are due to cells sensing and adapting to high oxygen levels. The increased levels of oxygen provided in a hyperbaric chamber increases vascular growth and stops chronic inflammation, reducing severe side effects.

For the oxygen treatments, participants spent 90 minutes a day in a hyperbaric chamber on 30-40 occasions, at a pressure of 1.4 atmospheres (equivalent to 14m underwater). The control group received the usual treatment, which normally includes medication and physiotherapy, for example.

The capacity already exists today

“We have reason to believe that there are many patients with severe symptoms who are never referred to hyperbaric oxygen therapy. Today we already have the capacity to treat more patients, but we need to be better at sharing our knowledge with our colleagues and with patient associations,” says Nicklas Oscarsson.

Severe side effects after radiation therapy are one of the main limitations on the dose of radiation that can be given in cancer treatment. The availability of a treatment that can reduce the number of people affected by these side effects opens the door to increased radiation doses and thus more curable tumours. One area for further investigation, according to the researchers, is whether early treatment with hyperbaric oxygen can prevent the occurrence of severe side effects.

The results are based on surveys and analyses of the participants who have been involved all the way, 70 adults. The treatments were conducted at five university hospitals in the Nordic countries: Rigshospitalet in Denmark, Turku in Finland, Haukeland in Norway, and Karolinska and Sahlgrenska in Sweden.

Source: University of Gothenburg

Preventing Unnecessary Pancreatic Cancer Surgery

Pancreatic cancer. Credit: Scientific Animations CC BY-SA 4.0

Pancreatic cysts are fluid-filled sacs that can form in the pancreas. Some remain benign, while others have the potential to develop into pancreatic cancer. A recent study, which followed 257 patients in Japan for an average of five years, showed that the presence or absence of invasive nodules in pancreatic cysts is key to assessing whether these cysts are benign or cancerous.

The findings, published in the journal Annals of Surgery, may help patients diagnosed with a high risk of pancreatic cancer to avoid unnecessary surgery.

Pancreatic cancer is one of the most life-threatening and rapidly growing cancers. Pancreatic cysts, known as pancreatic intraductal papillary mucinous neoplasms (IPMNs), are gaining attention as one of the precursors of the cancer that can be identified by radiological imaging. In this context, patients diagnosed with pancreatic cysts are referred for further evaluation, and if they meet the criteria for being at particularly high risk of developing cancer, called high-risk stigmata, they are often recommended for surgery.

However, it was not clear whether all patients who met the criteria would need to undergo surgery. “In fact, among patients who underwent surgery, there were a number of cases where pathological examination results showed that their IPMNs were still benign and had not progressed to cancer,” explained Ryohei Kumano from Nagoya University, the first author of the study. “Pancreatic surgery is a significant burden for patients, so we wanted to find a more accurate way to diagnose whether their IPMNs are benign or cancerous in order to avoid unnecessary surgery.”

A research group consisting of Professor Hiroki Kawashima and Dr Kumano from Nagoya University Graduate School of Medicine, Professor Eizaburo Ohno from Fujita Health University, and their colleagues focused on the presence or absence of invasive nodules in 257 IPMN patients with high-risk stigmata. The researchers evaluated the prognosis of the patients with and without these nodules.

Invasive nodules, solid growths within cysts that have begun to invade surrounding tissues, are difficult to detect with a conventional method that uses a CAT scan. Therefore, the researchers instead used contrast-enhanced endoscopic ultrasound, which is thought to detect invasive nodules more accurately.

To track the prognosis of patients with and without invasive nodules between surgical and non-surgical groups, the researchers followed them for an average of about five years (ranging from 6 months to 24 years, depending on the patient).

The results showed that the presence or absence of invasive nodules had a significant impact on their survival. For patients with invasive nodules, undergoing surgery had a positive effect on improving their survival. On the other hand, most patients without invasive nodules had a favorable outcome even without surgery. 

Endoscopic ultrasound (EUS) enables differentiation between non-invasive and invasive nodules within IPMN, providing crucial information for surgical decision making. (Credit: Ryohei Kumano) 

In this study, a total of 21 patients who did not have invasive nodules opted for clinical monitoring instead of surgery. Notably, their five-year survival rates were 84.7% for overall survival and 100% for disease-specific survival.

In addition, in patients at higher risk for surgery, such as the elderly, there was little difference in survival rates between patients who underwent surgery and those who did not, if they had no invasive nodules. “Avoiding surgery, especially in such patients, seems to be a reasonable treatment strategy, given the fact that pancreatic surgery is highly invasive, carries a high risk of complications, and requires a long recovery period,” Kumano said.  

“We expect that our findings will contribute to future clinical guidelines for IPMNs, leading to more accurate cancer diagnosis and optimised treatment selection.”

Source: Nagoya University

Statin Use May Improve Survival in Patients for Some Blood Cancers

Photo by Towfiqu Barbhuiya on Unsplash

Patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) who were taking cholesterol-lowering statin medications at the start of their cancer treatment had a 61% lower risk of dying from their cancer compared to similar patients who were not taking statins, according to a study published today in the journal Blood Advances.

“This is the first systematic evaluation of the association of statin use with survival outcomes in patients with CLL or SLL who have been treated with contemporary targeted agents such as ibrutinib,” said the study’s principal investigator, Ahmad Abuhelwa, PhD, an assistant professor of pharmacy practice and pharmacotherapeutics at the University of Sharjah in the United Arab Emirates. “Our results highlight a strong link between statin use and improved survival in this patient population.”

CLL is a slow-growing cancer that starts in the blood-forming cells of the bone marrow and is the most common form of leukaemia in adults in the United States. SLL, also a slow-growing cancer, affects the same type of cells as CLL but starts in lymphoid tissues such as the spleen instead of in the blood-forming cells.

Statins are among the most widely prescribed medications. It’s estimated that over 90 million adults in the United States take a statin drug to reduce their cholesterol levels and lower their risk for heart disease, which can lead to heart attacks or strokes. Previous studies have linked statin use to reduced death rates from several cancers, including CLL, said Dr Abuhelwa. However, those studies did not evaluate the effects of statin use in patients who were treated with newer cancer therapies such as the targeted drug ibrutinib, he said.

In the current study, Dr Abuhelwa and his colleagues analysed data from 1467 patients with CLL or SLL who participated in four international clinical trials conducted between 2012 and 2019. In these trials, patients were randomly assigned to treatment with ibrutinib either alone or in combination with other anti-cancer drugs, or to a drug regimen that did not include ibrutinib. A total of 424 patients (29%) were taking a statin at the time they started treatment across the four clinical trials. The median patient age was 65, and 66% were men; 92% had CLL, which was either newly diagnosed, had come back, or had not responded to prior treatment.

The study’s primary endpoints were cancer-specific survival (how long patients lived after starting treatment before dying specifically from their cancer), overall survival (how long patients lived after starting treatment, regardless of the cause of death), and progression-free survival (how long patients lived after starting treatment before their cancer worsened or they died from any cause). The secondary endpoint was the proportion of patients who experienced severe or life-threatening adverse events. The median follow-up time for all patients enrolled in the four trials was five years for overall survival and 22 months for progression-free survival.

To account for potential confounding factors, the investigators adjusted their analysis for variables including each patient’s diagnosis, age, sex, weight, physical functioning (as assessed by doctors), disease severity, length of time since their diagnosis, number of co-existing illnesses, use of other medications for heart conditions or high blood pressure, and the specific anti-cancer treatment regimen received.

Results showed that, regardless of any of these factors, patients who took a statin had, on average, a 61% reduced risk of dying from their cancer, a 38% reduced risk of death from any cause, and a 26% reduced risk of disease progression. Importantly, statin use did not increase the likelihood of severe or life-threatening adverse events.

“These findings don’t allow us to say for certain that statins directly improve cancer outcomes,” said Dr. Abuhelwa. “However, the fact that this association remained strong even after accounting for multiple factors makes it an important area for future research.” As next steps, he recommended conducting laboratory studies to better understand how statins may influence cancer biology, as well as prospective clinical trials in which patients with CLL or SLL are randomly assigned to take a statin or not.

The study has several limitations given its observational nature. For example, patients enrolled in clinical trials tend to be monitored more closely than those who receive treatment outside of a clinical trial, so the study findings may not be generalizable to patients treated in non-clinical trial settings. Additionally, because patients used various statins at different doses, the study could not determine the effects of specific statin types, doses, or duration of use on patients’ survival.

“While our results are very promising, we can’t recommend starting statins for CLL/SLL treatment based on this study alone,” Dr Abuhelwa said. “Future clinical trials are needed to determine definitively whether statins have a direct benefit on cancer survival.”

Source: American Society of Hematology

Research Identifies the Key to Pancreatic Cancer’s Extreme Aggressiveness

Pancreatic cancer. Credit: Scientific Animations CC BY-SA 4.0

Pancreatic cancer is one of the most aggressive cancers and has one of the lowest survival rates: only 10% after five years. One of the factors contributing to its aggressiveness is its tumour microenvironment, known as the stroma, which makes up the bulk of the tumour mass and consists of a network of proteins and different non-tumour cells. Among these, fibroblasts play a key role, helping tumour cells to grow and increasing their drug resistance.

Now, a study led by researchers from the Hospital del Mar Research Institute and other institutions has identified a new key factor contributing to this feature of pancreatic cancer: a previously unknown function of Galectin-1 protein inside the nuclei of fibroblasts. This discovery, published in the journal PNAS, offers new insights into the role of these cells in the progression of pancreatic cancer.

“The stroma is considered a key component in the aggressive nature of pancreatic cancer, as it interacts with tumour cells, protects them, and hinders the action of drugs. Moreover, stromal cells, particularly fibroblasts, produce substances that support tumour growth and dissemination,” explains Dr Pilar Navarro, coordinator of the Cancer Molecular Targets Research Group at the Hospital del Mar Research Institute and IIBB-CSIC-IDIBAPS. Until now, fibroblasts were known to secrete Galectin-1, a protein with pro-tumour properties. This study, however, shows that the molecule is also located inside fibroblasts-specifically in their nuclei-where it plays a key role in gene expression regulation.

The presence of this molecule activates fibroblasts, making them support tumour cell development. The researchers also discovered that “Galectin-1 can regulate gene expression in these cells at a highly specific level without altering the DNA sequence, through epigenetic control. One of the genes it regulates is KRAS, which plays a critical role in pancreatic tumours,” explains Dr Navarro. This gene is also present in tumour cells in 90% of patients, though in this case it is mutated. It is considered one of the main drivers of uncontrolled growth and tumour aggressiveness.

Designing new strategies

The team behind the study had previously identified the prominent role of Galectin-1 in pancreatic cancer. The newly discovered functions now pave the way for developing new strategies to tackle this type of tumour. “Until now, efforts have focused on inhibiting Galectin-1 secreted by the stroma surrounding the tumour. Now, we see that we also need to block the protein inside the fibroblast nuclei,” says Dr Neus Martínez-Bosch, researcher at the Hospital del Mar Research Institute. “We need to find new inhibitors that work inside fibroblasts, not just on the protein they secrete,” she adds.

To carry out the study, researchers worked with tissue samples from pancreatic cancer patients, allowing them to analyse the presence and function of Galectin-1 in fibroblast nuclei. They also performed in vitro experiments with human fibroblast cell lines, investigating the effects of inhibiting both the protein and the KRAS gene, and observed deactivation of these cells-effectively halting their cooperation with tumour cells.

Dr. Judith Vinaixa, also a researcher at the Hospital del Mar Research Institute and first author of the study, highlights the importance of these results: “We have confirmed the key role of Galectin-1 in the fibroblast cell nucleus, where it regulates the expression of multiple genes critical for cell behaviour.”. Dr. Gabriel Rabinovich, researcher at IBYME (CONICET) and the CaixaResearch Institute, adds: “The next steps will involve exploring therapeutic combinations that inhibit both extracellular and intracellular Galectin-1. This protein also participates in key processes such as blood vessel formation and resistance to immunotherapy. Therefore, this strategy becomes particularly relevant given the multiple antitumoral effects of Galectin-1 inhibition.”

Source: IMIM (Hospital del Mar Medical Research Institute)