Category: Cancer

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Space-age Lessons Could Protect Childhood Cancer Survivors’ Bone Health

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Corresponding author Kiri Ness, PT, PhD, FAPTA, St. Jude Department of Epidemiology and Cancer Control, working with a patient.

Space has inspired and delighted people for centuries. The much-anticipated advent of crewed spaceflight taught invaluable lessons, even for the most unexpected groups back on terra firma. In the 1960s, astronauts returned from microgravity with decreased bone density. This decrease revealed that bones must undergo constant stress to grow and maintain themselves.

Survivors of childhood cancer, while seemingly unrelated to astronauts in the weightlessness of space, are one group unexpectedly impacted by this revelation. These two distinct groups share a connection in the loss of bone density occurring during a significant life event. Children receiving cancer treatment are often sedentary due to their therapy. Their listlessness mimics microgravity’s effect on astronauts, while the treatment itself may also negatively impact their bone health.

Recent research spearheaded by first author Chelsea Goodenough, PhD, St. Jude Department of Epidemiology and Cancer Control, characterised bone mineral density loss in survivors of childhood cancer. Published in JAMA Network Open, her study looked at survivors five or more years after treatment using the St. Jude Lifetime Cohort Study (St. Jude LIFE). She found that survivors were more likely than age-matched peers to experience low bone mineral density. Low bone mineral density predicted a higher chance of lacking independence, including being unemployed or requiring a personal care attendant, highlighting the need to find ways to intervene to protect and promote survivors’ bone health.

“Glucocorticoids given during cancer therapy can act as a giant hammer to bone mineral density,” said corresponding author Kiri Ness, PT, PhD, FAPTA, St. Jude Department of Epidemiology and Cancer Control. “We found that this loss could have long-term consequences for survivors. We saw 30-year-olds that functionally looked like they were in their 70s and 80s, showing the need for early interventions after treatment.”  

Modifiable factors influence survivors’ bone mineral density

“The unique aspect of this study is that we calculated the extent to which different factors contributed to loss of bone density,” Ness said. “That gives us a starting place to design interventions.”

Bone loss decades after treatment could be related to therapy, something investigators can’t change after the fact, but potentially modifiable factors could also be contributing. The St. Jude researchers wanted to see if they could identify any modifiable factors that could point to protective interventions for further investigation.

“We found that about 33% of bone density loss was due to cranial radiation for those who received it,” Ness explained. “But about 25% of the deficit was related to hormone deficiencies, such as hypogonadism.” Hypogonadism is a common consequence of childhood cancer therapy. During treatment, the patient receives hormone-disrupting chemicals, sometimes resulting in an extended deficiency of testosterone or oestrogen and human growth hormone. These three hormones are known to have significant impacts on bone health. Since hormone replacement therapies already exist, the study has identified an area for potential pharmaceutical intervention to address hypogonadism to improve bone density among survivors of childhood cancer. 

Lifestyle changes can impact bone health

“Compared to hypogonadism, smoking and sedentary behaviour were responsible for a smaller but still significant decrease in bone density,” Ness said. “But we already have interventions for both; we just need to test them for their effect on bone mineral density.”

Sedentary behaviour is a common experience during treatment. “Understandably, kids don’t feel good during cancer therapy,” Ness explained. “So, they lay in bed.” Lying in bed acts like microgravity: The kids don’t put stress on their bones, resulting in bone loss. However, survivors can prevent this with physical activity. Exercise has already been shown to help protect cardiovascular health among survivors, so the research provides another potential motivation for exercise.

Ness, whose research focuses on lifestyle interventions to support survivors of childhood cancer, already promotes the positives of physical activity. Her insistence, bolstered by this study, has gained her a reputation among patients. “The kids on the floor call me the ‘exercise lady,’” Ness proudly acknowledged. “When they see me, they say, ‘Here she comes, the exercise lady is here.’”

Physical activity to improve bone health could be as simple as jumping or as elaborate as a dedicated heavy weight-lifting programme. The increased activity will likely promote bone maintenance and, hopefully, growth, a parallel to the exercise programme astronauts undergo upon returning from space to re-establish their bone mass.

While exercise is one way in which survivors can improve their bone health, the study also suggested that those who develop a smoking habit may have one more reason to quit. Survivors who smoked were more likely to have a moderate or severe bone mineral density deficit, along with a host of other problems.

“Smoking is just a bad idea for survivors,” Ness said. “Smoking causes a lot of ill effects, not just bone loss. So, we need to encourage young cancer survivors never to start and give cessation interventions to those that have.” Over 20% of survivors in the study currently smoked, indicating a significant opportunity for intervention.

Better understanding means more chances to help

By attributing the sources of bone mineral density loss, the St. Jude scientists have created a roadmap for exploring potential interventions. The ultimate goal is to give survivors of childhood cancer as much independence as possible to take control of their futures.

“I want survivors to know that if they have low bone mineral density, it’s not an insurmountable problem,” Ness said. “You can be proactive – by being physically active, avoiding smoking and making sure your physician understands your chronic health condition. That’s how you give yourself the best chance of having an independent life as an adult, chasing your dreams.” 

Maybe, one day, they could even become an astronaut.

Written by Alex Generous, PhD.

Source: St. Jude Children’s Research Hospital

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Newly Discovered Cancer Cell Energy Pathway Blocked with Compound in Ginger

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Photo by TUMERI on Unsplash

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.

Source: Osaka Metropolitan University

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Y Chromosome Loss in Immune Cells Creates Opportunity for Cancers

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Scanning electron micrograph of a T cell lymphocyte. Credit: NIH / NIAID

A study initiated by a University of Arizona Comprehensive Cancer Center physician-scientist has for the first time defined how loss of the Y chromosome in male immune cells negatively affects immune system function. The findings, published in Nature, may explain why loss of Y is associated with lower cancer survival rates.

In males, each cell in the body usually contains one X and one Y chromosome. “Loss of Y” is a common, nonhereditary genetic change in men in which an immune cell in the blood loses its Y chromosome. It is often associated with aging. Loss of Y has been linked to increased mortality from carcinomas for many years, though no one knew why.

This study is the first to identify and define the relationship between loss of Y in white blood cells, immune cells and tumours, providing insights as to why men with loss of Y have increased cancer risks and poorer outcomes.

“These findings represent a big step forward in our understanding of why men with loss of Y in their blood cells have a higher mortality from cancer. It turns out it’s because these cells make the immune system infiltrating the cancer less effective,” said Dan Theodorescu, MD, PhD, director of the Cancer Center and a professor in the College of Medicine – Tucson. 

“We hope this provides a solid lead and framework for the nascent Y chromosome field to pursue so we can collectively better understand all the possible biological implications of this finding and how to use them to develop more effective approaches in prevention, treatment resulting in higher survival rates for patients.”

The research team discovered that loss of the Y chromosome – previously identified in malignant epithelial cells by the Theodorescu lab – also occurred in nearby noncancerous tissues, including connective tissue and immune cells.

Most notably, the team found that this chromosomal loss in helper and cytotoxic T cells, which are responsible for attacking cancer cells, was associated with a reduced ability to kill those cancerous cells. The findings suggest a mechanism by which tumours may evade immune detection and suppression.

Finally, the research team found that loss of Y in epithelial cells, combined with loss of Y in T cells, resulted in more aggressive cancers and lower survival rates in patients.

“The study has potential implications for current immunotherapies, including CAR T therapy,” Theodorescu said. “Further research is clearly needed but perhaps immunotherapies using cells from a patient’s immune system could be screened for loss of Y before being used in treatment.”

Source: University of Arizona

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Zapping Glioblastoma With Electric Fields Slows Tumour Growth

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Source: Pixabay

A new study led by Keck Medicine of USC researchers may have uncovered an effective combination therapy for glioblastoma, a brain tumour diagnosis with few available effective treatments. According to the National Brain Tumor Society, the average survival for patients diagnosed with glioblastoma is eight months.

The study, which was published in the journal Med, finds that using Tumour Treating Fields therapy (TTFields), which delivers targeted waves of electric fields directly into tumours to stop their growth and signal the body’s immune system to attack cancerous tumour cells, may extend survival among patients with glioblastoma, when combined with immunotherapy (pembrolizumab) and chemotherapy (temozolomide).

TTFields disrupt tumour growth using low-intensity, alternating electric fields that push and pull key structures inside tumour cells in continually shifting directions, making it difficult for the cells to multiply. Preventing tumour growth gives patients a better chance of successfully fighting the cancer. When used to treat glioblastoma, TTFields are delivered through a set of mesh electrodes that are strategically positioned on the scalp, generating fields at a precise frequency and intensity focused on the tumour. Patients wear the electrodes for approximately 18 hours a day.

Researchers observed that TTFields attract more tumour-fighting T cells, which are white blood cells that identify and attack cancer cells, into and around the glioblastoma. When followed by immunotherapy, these T cells stay active longer and are replaced by even stronger, more effective tumour-fighting T cells.

“By using TTFields with immunotherapy, we prime the body to mount an attack on the cancer, which enables the immunotherapy to have a meaningful effect in ways that it could not before,” said David Tran, MD, PhD, chief of neuro-oncology with Keck Medicine, co-director of the USC Brain Tumor Center and corresponding author of the study. “Our findings suggest that TTFields may be the key to unlocking the value of immunotherapy in treating glioblastoma.”

TTFields are often combined with chemotherapy in cancer treatment. However, even with aggressive treatment, the prognosis for glioblastoma remains poor. Immunotherapy, while successful in many other cancer types, has also not proved effective for glioblastoma when used on its own.

However, in this study, adding immunotherapy to TTFields and chemotherapy was associated with a 70% increase in overall survival. Notably, patients with larger, unresected (not surgically removed) tumours showed an even stronger immune response to TTFields and lived even longer. This suggests that, when it comes to kick-starting the body’s immune response against the cancer, having a larger tumour may provide more targets for the therapy to work against.

Using alternating electric fields to unlock immunotherapy

Pembrolizumab, the immunotherapy used in this study, is an immune checkpoint inhibitor (ICI), which enhances the body’s natural ability to fight cancers by improving T cells’ ability to identify and attack cancer cells.

However, there are typically few T cells in and around glioblastomas because these tumours originate in the brain and are shielded from the body’s natural immune response by the blood-brain barrier. This barrier safeguards the brain by tightly regulating which cells and substances enter from the bloodstream. Sometimes, this barrier even blocks T cells and other therapies that could help kill brain tumours.

This immunosuppressive environment inside and around the glioblastoma is what makes common cancer therapies like pembrolizumab and chemotherapy significantly less effective in treating it. Tran theorised the best way to get around this issue was to start an immune reaction directly inside the tumour itself, an approach known as in situ immunisation, using TTFields.

This study demonstrates that combining TTFields with immunotherapy triggers a potent immune response within the tumour – one that ICIs can then amplify to bolster the body’s own defence against cancer.

“Think of it like a team sport – immunotherapy sends players in to attack the tumour (the offence), while TTFields weaken the tumour’s ability to fight back (the defence). And just like in team sports, the best defence is a good offence,” said Tran, who is also a member of the USC Norris Comprehensive Cancer Center.

Study methodology and results

The study analysed data from 2-THE-TOP, a Phase 2 clinical trial, which enrolled 31 newly diagnosed glioblastoma patients who had completed chemoradiation therapy. Of those, 26 received TTFields combined with both chemotherapy and immunotherapy. Seven of these 26 patients had inoperable tumours due to their locations – an especially high-risk subgroup with the worst prognosis and few treatment options.

Patients in the trial were given six to 12 monthly treatments of chemotherapy alongside TTFields for up to 24 months. The number and duration of treatments were determined by patients’ response to treatment. The immunotherapy was given every three weeks, starting with the second dose of chemotherapy, for up to 24 months.

Patients who used the device alongside chemotherapy and immunotherapy lived approximately 10 months longer than patients who had used the device with chemotherapy alone in the past. Moreover, those with large, inoperable tumours lived approximately 13 months longer and showed much stronger immune activation compared to patients who underwent surgical removal of their tumours.

“Further studies are needed to determine the optimal role of surgery in this setting, but these findings may offer hope, particularly for glioblastoma patients who do not have surgery as an option,” said Tran.

The researchers are now moving ahead to a Phase 3 trial.

Source: University of Southern California – Health Sciences

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Closure of US-funded Cancer Clinic Further Burdens Public Hospitals

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The Cervical Cancer Screening and Prevention Clinic at Helen Joseph Hospital in Johannesburg was forced to shut down in mid-May after losing all its funding from the US President’s Emergency Plan for AIDS Relief (PEPFAR). Photos: Elna Schütz

By Elna Schütz

Hundreds of cervical cancer patients will likely be referred to overburdened hospitals following the closure of the Cervical Cancer Screening and Prevention Clinic at Helen Joseph Hospital in Johannesburg.

Following over 20 years of operations, the clinic was forced to shut down in mid-May after losing all its funding from the US President’s Emergency Plan for AIDS Relief (PEPFAR). It relied on some financial reserves to taper its activities over several months. Most clinic staff have been let go.

The clinic served women who were referred from across Johannesburg and as far as Springs. A significant part of that group lives with HIV.

“Many of these women are from underserved communities with limited access to specialist care,” says Dr Mark Faesen, Specialist Gynaecologist with the Clinical HIV Research Unit (CHRU).

The clinic offered critical cervical cancer screening and follow-up services, including Pap smears and colposcopies – a cervical examination for abnormalities. The clinic was managing around 1,400 patients annually. “It served as a clinical and research hub, preventing many cancers,” Faesen says.

We spoke to Zinhle (name changed) who was screened at the clinic after feeling ill for a year and who sought help at four different hospitals.

“When I got [to this clinic], I was received with a warm welcome,” she says, emphasising that every step of the process was explained to her and she was made to feel comfortable. “Where else are we supposed to go?”

Zinhle says she is deeply upset that she can no longer be treated at the clinic if she needs it again.

Faesen says the clinic’s closure will put immense pressure on other public hospitals offering these services, like Rahima Moosa or Chris Hani Baragwanath. This is likely to lead to longer waiting times for screening, diagnosis and treatments. “Early detection is important,” Faesen says. “Without timely diagnosis, outcomes are far poorer.”

Lorraine Govender, the National Manager of Health Programmes at the Cancer Association of South Africa (CANSA) says they are deeply concerned by the closure, as it is a serious setback in the ongoing fight against the disease.

Cervical cancer is the second most common cancer in women in South Africa, and results in the most deaths. It is curable if diagnosed and treated early. A Human Papillomavirus (HPV) vaccination also reduces the risk of cervical cancer. While low screening rates and backlogs in treatment have been long-standing across the country, Johannesburg appears to be particularly burdened. The shutdown of this clinic adds to a larger shortage of screening and treatment in Gauteng.

The Department of Health has previously stated that while it has improved vaccination efforts against cervical cancer, “screening and treatment are lagging behind”. The national health policy calls for women aged 30 to 50 to be screened at least three times in their lives. Women living with HIV should be screened at least every three years.

Cervical cancer screening services are limited and overwhelmed at most public hospitals, Faesen says. “The funding cuts have a knock-on effect: increasing patient loads at the few remaining colposcopy clinics.”

Lorraine Govender, the National Manager of Health Programmes at the Cancer Association of South Africa (CANSA) says they are deeply concerned by the closure, as it is a serious setback in the ongoing fight against the disease.

“Cervical cancer is both preventable and treatable when detected early, making continued access to screening services vital … The closure of this Johannesburg clinic must be a call to action,” Govender says.

Faesen stresses the urgent need for increased funding for decentralised screening services to fill the gaps created by clinics like the one at Helen Joseph Hospital. “Equipping more public sector sites with colposcopy capability and training personnel is also essential.”

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Read the original article.

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New Findings Reveal Immune Molecules that Drive Inflammatory Bowel Disease

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Irritable bowel syndrome. Credit: Scientific Animations CC4.0

Chronic inflammatory bowel disease is challenging to treat and carries a risk of complications, including the development of bowel cancer. Young people are particularly affected: when genetic predisposition and certain factors coincide, diseases such as ulcerative colitis or Crohn’s disease usually manifest between the ages of 15 and 29 – a critical period for education and early career development. Prompt diagnosis and treatment are crucial. Researchers at Charité – Universitätsmedizin Berlin have now discovered a therapeutic target that significantly contributes to halting the ongoing inflammatory processes. Their findings are published in the current issue of the journal Nature Immunology*.

Sometimes gradually, sometimes in flare-ups – accompanied by severe abdominal cramps, diarrhoea, weight loss, fatigue and a high level of emotional stress – this is how the two most common chronic inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, often begin. While ulcerative colitis only affects the inner lining of the large intestine, Crohn’s disease can involve the entire thickness of the intestinal wall, most commonly in the small intestine, but sometimes also the stomach and oesophagus. Ongoing inflammation can cause lasting tissue damage and increase the risk of cancer. While traditional treatments aim to suppress the immune system as a whole, newer therapies are more targeted: they interrupt the inflammatory process by blocking specific messenger substances that drive inflammation in the body.

The exact causes of severe systemic diseases are still not fully understood. In addition to genetic factors, environmental influences are also believed to play an important role in their development. Prof Ahmed Hegazy has been studying inflammatory processes in the gut and the immune system’s defence mechanisms at Charité’s Department of Gastroenterology, Infectiology and Rheumatology for several years. Together with his team, he has now succeeded in identifying the interaction between two messenger substances of the immune system as the driving force behind chronic intestinal inflammation: Interleukin-22, a protein that supports the cells lining the inside of the gut and helps maintain the protective barrier, and oncostatin M, a signalling molecule that plays a significant role in tissue repair and cell differentiation.

Uncontrolled chain reaction

“At the clinic, we mainly see young patients who just beginning their professional lives. So far, we have only been able to slow down the progression of the disease and alleviate symptoms. But not all patients respond well to existing treatments, so new therapeutic approaches are urgently needed,” says Ahmed Hegazy. In previous work, the research team closely examined the effects of oncostatin M, an inflammation-promoting messenger molecule. This protein, produced by certain immune cells, activates other inflammatory factors – setting off a chain reaction that triggers an excessive immune response. “It was especially interesting for us to see that patients with high levels of oncostatin M do not respond to several common therapies,” Ahmed Hegazy explains. “This means that Oncostatin M levels could help predict treatment failure and may serve as a biomarker for more severe disease. That’s exactly where we focused our efforts: we wanted to understand this signaling pathway better and find ways to block it with targeted treatments.”

The research team spent five years uncovering how the immune messenger oncostatin M triggers inflammatory responses. They began by using animal models, and later studies tissue samples from patients, to examine the different stages of chronic intestinal diseases, State-of-the-art single-cell sequencing showed that – compared to healthy tissue – a much larger number of unexpected cell types in the inflamed gut have receptors for oncostatin M. At the same time, additional immune cells start producing the inflammatory protein. Interestingly, interleukin-22, which normally protects tissue, also makes the gut lining more sensitive to oncostatin M by increasing the number of its receptors. “These two immune messengers work together and amplify the inflammation, drawing more immune cells into the intestine, like a fire that keeps getting more fuel and spreads,” as Ahmed Hegazy relates. “In our models, we specifically blocked the binding sites for oncostatin M and saw a clear reduction in both chronic inflammation and the associated of cancer.”

Targeted therapy for high-risk patients in sight

The researchers found a particularly high number of receptors for the messenger molecule oncostatin M around the tumours in tissue samples from patients with colorectal cancer caused by chronic intestinal inflammation, but not in the surrounding healthy tissue. This observation suggests that this signalling pathway may help promote cancer development. But chronic inflammation does not always lead to bowel cancer, and not every patient is affected in the same way, making treatment and prognosis difficult. With an understanding of oncostatin M’s amplifying effect on interleukin-22, new therapies may be possible.

The team’s experimental findings may soon translate into a real-world therapy: by specifically disrupting the harmful interaction between the immune messengers interleukin-22 and oncostatin M. “Our results provide a strong scientific basis for developing targeted treatments against this inflammation-promoting mechanism in chronic inflammatory bowel disease — particularly in patients with more severe forms of the illness,” explains Ahmed Hegazy. A clinical trial is already underway to test an antibody that blocks the receptors for Oncostatin M.

Source: Charité – Universitätsmedizin Berlin

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Immune System the Focus of PhD’s Research at UKZN

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Elated at graduating with a doctoral degree is Dr Aviwe Ntsethe. Credit: University of KwaZulu-Natal

Dr Aviwe Ntsethe’s curiosity in the Medical field deepened when he started exploring the complexities of human physiology and the crucial role of the immune system in cancer, leading to him graduating with a PhD.

Growing up in the small town of Bizana in the Eastern Cape, Ntsethe attended Ntabezulu High School, where his passion for Medical Science took root. Despite facing significant challenges, including limited funding opportunities for his studies, he remained determined to advance in the discipline.

Throughout his PhD journey at UKZN, Ntsethe had to juggle multiple jobs to support himself and his studies while conducting his research. He worked at Netcare Education and the KwaZulu-Natal College of Emergency Care, and later took up a position as a contractual laboratory technician in the Department of Physiology at UKZN. It was with the guidance of his PhD supervisor, Professor Bongani Nkambule, that he learned critical work ethics and advanced laboratory techniques. The co-supervision of Professor Phiwayinkosi Dludla further enriched his research experience and contributed to his academic growth.

Ntsethe’s thesis focused on investigating B cell function and immune checkpoint expression in patients with Chronic Lymphocytic Leukaemia (CLL). The study found that patients with CLL had higher levels of immune checkpoint proteins in their B cell subsets, which play a crucial role in regulating the immune system.

Furthermore, using monoclonal antibodies that target these immune checkpoints, he found these patients could potentially benefit from immunotherapy. Specifically, immunotherapy may improve the function of B cells, key players in fighting infections and cancers, thereby offering new hope for better outcomes in patients with CLL.

He has published three papers from this study. ‘I am excited and proud when I reflect on my achievement of completing this significant journey which was both challenging and rewarding, pushing me to expand my knowledge and skills in ways I never imagined.’

Now, a lecturer at Nelson Mandela University, Ntsethe is committed to mentoring the next generation of Medical scientists. He continues to use the invaluable knowledge and experience he gained during his PhD studies to inspire students and cultivate their passions in research and health sciences. Looking ahead, Ntsethe hopes to expand his research, focusing on immune system interactions in chronic diseases while also encouraging students from diverse backgrounds to pursue careers in Medical Science.

Outside academia, Ntsethe enjoys travelling, staying physically active through workouts, playing chess and indulging in coding or programming.

Source: University of KwaZulu-Natal

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Do Bevacizumab’s Ovarian Cancer Clinical Trial Results Hold up in the Real World?

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Photo by Tima Miroshnichenko on Pexels

A real-world study based on information from an electronic health records–derived database reveals limited benefits of adding bevacizumab to first-line chemotherapy for patients with ovarian cancer, consistent with previous clinical trials. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

Bevacizumab is a monoclonal antibody against vascular endothelial growth factor A that acts to inhibit malignant cell growth and blood vessel formation. It’s approved as a treatment for various types of cancer. In clinical trials of patients with ovarian cancer, adding bevacizumab to first-line chemotherapy did not prolong overall survival compared with chemotherapy alone, but this treatment strategy did improve overall survival in analyses limited to patients with high-risk prognostic factors—such as those with advanced disease and those who had residual cancer present after surgery. A final long-term analysis did not find an overall survival benefit associated with bevacizumab in the full patient cohort.

To investigate whether these findings also hold true in real-world clinical practice, researchers examined the electronic health records of 1,752 patients with stage III or IV ovarian cancer who initiated chemotherapy with or without bevacizumab in 2017–2023 and were followed for a median time of 1.5 years.

Among patients with high-risk prognostic factors, the median time to next treatment was significantly longer for those receiving chemotherapy plus bevacizumab compared with those receiving chemotherapy alone: 13.6 versus 11.7 months. (Time to next treatment is used to assess the duration of clinical benefit by measuring the time between initiating a treatment and starting the next line of therapy). In these patients, there was also a trend towards longer median overall survival for the combination therapy: 31.1 versus 27.4 months. Among patients without high-risk prognostic factors, outcomes did not differ with the addition of bevacizumab. Benefits therefore seemed limited to special subpopulations, mirroring the findings from clinical trials.

“Our results were similar to results from clinical trials,” said lead author Linda R. Duska, MD, MPH, of the University of Virginia School of Medicine. “Our findings suggest that clinicians should consider a patient’s risk factors before using bevacizumab with first-line chemotherapy in the treatment of advanced ovarian cancer.”  

Source: Wiley

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Localised Hypoxia Promotes Colon Cancer Growth

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Fig. 1. In healthy colon tissue, “good” fibroblasts help support tissue architecture. However, in colon cancer, these fibroblasts transform into “bad” fibroblasts in low-oxygen areas near the tumour surface. These “bad” fibroblasts block the formation of blood vessels, keeping their surroundings in an oxygen-deprived state, which supports their own survival. At the same time, they release growth-promoting factors that act like supplements for cancer cells. While it may seem unexpected that hypoxia supports tumour growth, this study reveals that localised hypoxic environments can accelerate cancer progression.

To effectively battle cancer, scientists must study the battlefield. Now, in a recent study published in Nature Communications, a multi-institutional research team including The University of Osaka has discovered some crucial intel: localised hypoxia in the colon cancer microenvironment can promote tumour growth.

Until recently hypoxia was thought to suppress tumour progression. Consequently, drugs that block the supply of oxygen to tumours were being used to treat cancers. But these treatments had mixed results; sometimes even accelerating tumour growth. Understanding why this happens has become an urgent question in cancer research.

“We uncovered a surprising mechanism by which hypoxia may promote tumour growth, and it involves the formation of cells called inflammatory fibroblasts,” explains lead author of the study, Akikazu Harada.

The research team found that when oxygen becomes scarce in certain areas of a colon tumour, the surrounding fibroblasts (normally ‘good’ cells that support tissue structure) transform into harmful inflammatory fibroblasts. The altered cells release factors that help tumours grow, such as epiregulin. In addition, they release Wnt5a protein, which helps maintain a low-oxygen state by inhibiting new blood-vessel formation at the site of its release, thereby maintaining hypoxia.

To validate the findings from the mouse model in human samples, the researchers pooled data from human samples obtained from patients with a healthy colon, colon cancer, and those with inflammatory bowel disease. Later, they analysed the data and compared their findings with data from mice.

“We found that the malignant transformation of fibroblasts and the induction of Wnt5a-secreting fibroblasts are commonly observed in both mouse models and human samples,” says Akira Kikuchi, senior author of the study.

This insight into the potential pathology of colon cancer and inflammation can provide the blueprints for a new cancer battle strategy: drug therapies that target Wnt5a-producing fibroblasts. As a result, fibroblasts are now being recognised as a key ‘third’ therapeutic target, complementing traditional treatments targeting cancer cells and immune cells.

This finding holds special importance for colon cancer, which is the leading type of cancer in Japan. Additionally, the observed pathological changes of fibroblasts could also apply to chronic inflammatory disorders like inflammatory bowel disease, offering fresh insights into their mechanisms and potential new treatment strategies for these challenging conditions.

Source: The University of Osaka

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New Study Reveals Why Common Leukaemia Treatments Fail in Some Patients

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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.

The study was published in Blood Cancer Discovery.

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.

Source: University of Colorado Anschutz Medical Campus