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Liver transplant added to chemotherapy improves survival in advanced colorectal cancer

The incidence of colorectal cancer continues to rise worldwide. Colorectal cancers originate in the bowel but have the potential to spread or metastasize to other organs. The most common site of spread of colorectal cancer is the liver and to date the most effective treatment for this surgery is to remove the liver, usually in combination with chemotherapy.  Unfortunately, only twenty percent of people with liver metastases from colorectal cancer will be able to have surgery to remove the cancer.  To date there have been no other treatments that offer a potential cure for people with liver metastases that cannot be surgically removed.

In this clinical trial people with liver metastases from colorectal cancer that are unable to be removed with surgery were randomized to receive either liver transplant and chemotherapy or chemotherapy alone.  Promisingly, those patients who underwent liver transplantation had better survival rates compared with those who did not. The combination of liver transplantation and chemotherapy may offer a potential cure to those people who would otherwise have a poor long-term outcome.



SOX17 enables immune evasion of early colorectal adenomas and cancers

Being able to treat colorectal cancer (CRC) with the right treatment and early is key to improving the health outcomes and long-term survival of patients. One of the ways cancers establish and progress is by blunting the immune defence. This study by Goto et al (2024) has shown that protein, SOX17, helps tumours escape the immune system in early tumour development. SOX17 plays a role in embryonic development and is not usually expressed in the healthy gut lining of adults. The researchers grew mini tumours with common CRC-associated mutations and transplanted them into the colons of mice. The researchers observed an increase in SOX17 expression and decreased cancer-fighting T cells and reduced activity of immune protein, interferon gamma. When the research team generated colorectal tumours that were unable to express SOX17, these tumours became susceptible to the anti-cancer immune response. These findings show that SOX17 is playing a role in the tumours ability to hide from the immune system. The research team validated that human colorectal cancers express SOX17 and, at higher levels in early CRC compared to late stage CRC, suggesting that SOX17 is important for tumour establishment and development by preventing immune surveillance.  

Next steps will involve identifying other proteins in this immunosuppressive pathway mediated by SOX17, which may reveal new therapeutic targets. In the bigger picture, it may be important to consider how early CRC and pre-cancerous growths are detected and how we can utilise ‘early’ treatments when they are needed. This study evidences a new immune evasion mechanism facilitated by SOX17 in the early stages of CRC development.


Promising new immune checkpoint inhibitor for colorectal cancer

In New Zealand, colorectal cancer (CRC) is the most diagnosed cancer and the second most common cause of death due to cancer. Overall survival rates of people are highly variable even with advancements in therapy. One form of therapy, known as immune checkpoint inhibitors (ICI), aims to reinvigorate the immune response to help destroy tumour cells. However, immune checkpoint inhibitors have only been effective in people with microsatellite instable high or mismatch repair deficient CRC, which represent about 4% of CRC types. ICI therapy has been elusive for the more common form of CRC known as the microsatellite stable CRC.

In a recently concluded phase 1 clinical trial, a new ICI botensilimab (antiCTLA4) was used in conjunction with balstilimab (antiPD1) was studied for safety in patients with microsatellite stable CRC that were not responding to chemotherapy. The study involved 101 patients that were followed for 6 months after receiving therapy. Promisingly, 61% of the patients had some form of response (either tumour shrinkage or stable disease). Furthermore, the most common side effects reported by the patients in the study were diarrhoea and fatigue. The treatment modality has now entered into late-stage clinical trials.



Gut microbiome signatures modulate cardiovascular disease risk

Cardiovascular disease related death remains the biggest killer worldwide, and despite knowledge of the In a new study from China, researchers have identified a relationship between the gut microbiome, metabolism and cardiovascular disease risk.
Using a discovery cohort of 10,207 individuals aged between 40-93 years, they identified five metabolic clusters, ranging from metabolically healthy to hyperglycaemic.  Those individuals within the hyperglycaemic cluster had an increased risk by 75% for developing cardiovascular disease within an 11.1-year period. Additionally, the authors developed a gut microbial age metric using 55 age-specific microbial species, identifying that cardiovascular disease risk increases with microbial age.
The results from this study support modulating the microbiome of metabolically unhealthy older people to reduce cardiovascular disease risk.

New antibody treatment shows promise for coeliac disease

Coeliac disease affects millions of people worldwide yet the only current treatment for coeliac disease is through adherence to a strict gluten-free diet. This form of disease management is considered suboptimal as it is highly restrictive, difficult to maintain and does not always promote intestinal mucosal healing.

A recent study by the Japanese pharmaceutical company, Chugai Pharmaceuticals, has presented a successful antibody treatment, DONQ52 for coeliac disease. This treatment targets HLA-DQ2.5 gluten peptides that are present in 85% of individuals with the disease. By blocking gluten-specific T cells, DONQ52 prevents immune damage to the small intestine upon gluten ingestion in individuals with coeliac disease.

This study examined the gluten-specific immune response in blood samples from participants with coeliac disease following the consumption of wheat, rye and barley products. A significant reduction in the gluten-specific T cell response was observed. Importantly, treatment with DONQ52 did not affect the T cell responses to non-gluten antigens, making DONQ52 a promising drug candidate.

This research provides an exciting new targeted treatment for those with coeliac disease that could improve quality of life by reducing the need for a strict gluten-free diet.



Faecal microbial transfer and complex carbohydrates mediate protection against COPD

Chronic obstructive pulmonary disease (COPD) is a common cause of illness in around 500 million people worldwide. It is know that those with COPD have altered microbiomes compared to those without COPD, but the direct role of microbes in the pathogenesis of the disease are unclear.  A recent study using a mouse model of cigarette smoke induced COPD showed that faecal microbiota transplant (FMT) alleviated inflammation in COPR by improving the lung function and breathing, compared to mice that didn’t get a FMT. The research group then identified specific bacterial species that were associated with lung health. Next, they conducted a small human study to determine if altering the microbiome via a dietary intervention (using inulin) would improve symptoms in those with COPD. Compared to a placebo group, those given dietary inulin had an improved quality of life, which was linked to changes in microbiome composition. Overall, these results suggest that by altering the microbiome of those with COPD, disease symptoms and quality of life may improve.


Safina Gadeock awarded HRC Emerging Researcher Award

Congratulations to Dr. Safina Gadeock, who was one of the 13 researchers awarded the HRC Emerging Researcher, 2024 for her study on "Interferon-alpha targets as prognostic biomarkers for IBD patients". She aims to validate an innovative Type I Interferon (immunomodulatory molecules) biomarker panel to predict response to anti-TNFs in a cohort of NZ and US IBD patients; and elucidate the mechanism(s) driving Type I Interferon-dependent regenerative responses and epithelial barrier integrity in responsive IBD patients. This study will steer the development of an innovative biomarker panel that will help gastroenterologists tailor therapy for the approximately 50 per cent of non-responsive IBD patients.


Industrialised societies have less cellulose-digesting gut bacteria

Cellulose is a ubiquitous material in nature that makes up the cell wall of plants, and is a major component of dietary fibre. Animals such as cows and sheep have specialised digestive tracts containing ruminant bacteria that allow them to extract energy from cellulose. In 2003, it was confirmed that humans also have some gut bacteria that can process cellulose. These bacteria play an important role in supporting other bacteria in the gut to promote a healthy gut microbiome.

A recent study has shown that humans are host to many more of this variety of bacteria than previously known ­– some related to those found in livestock and some from our primate ancestors. It was also shown that these cellulose-digesting bacteria are being lost from industrialised societies, possibly due to our diets becoming lower in fibre. The authors suggest there may be potential for reintroduction or enrichment of cellulose-digesting bacteria in the gut through dietary changes.



First targeted therapy approved for metastatic colorectal cancer patients in more than a decade.

Fruquitinib has been approved by the U.S. Food and Drug Administration (FDA) to treat metastatic colorectal cancer in patients who have progressed from standard therapies, including chemotherapy and other targeted therapies. Targeted therapy is a type of cancer treatment that targets specific gene pathways and proteins that help cancer cells survive and grow. Fruquitinib is a selective kinase inhibitor that targets every vascular endothelial growth factor receptor (VEGFR). These receptors help the cancer form new blood vessels in a process called angiogenesis. This process allows the cancer to access the body’s nutrients. Fruquitinib specifically targets this process and will ‘starve’ the tumour of nutrients. This selectivity is important as the drug can be combined with other treatments. 

Fruquitinib, under the trade name FRUZAQLA, was approved after two phase 3 clinical trials; the FRESCO-2 trial, and the FRESCO trial, evaluating the drug in a combined cohort of 1100 patients, with the drug being safe and effective in 734 of those patients. Patients showed an increase in survival in both phase 3 trials of around 3 months compared to placebo. Targeted therapies are not funded by PHARMAC in New Zealand for metastatic colorectal cancer. Certain targeted therapies, such as Fruquitinib may be covered by health insurance or are available to patients under a cost-share program from treatment manufacturers, such as Roche. Patients in New Zealand should consult with a specialist in private care to see if they will benefit from targeted treatment. 

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Andy Highton awarded Kia Niwha Leader Fellowship

Congratulations to Gut Health Network member, Andy Highton, who was awarded a Kia Niwha Leader Fellowship


Vedolizumab supports intestinal stem cell recovery.

A recent study from the University of California, San Francisco showed that Vedolizumab (VDZ), an anti-integrin antibody, effective in the treatment for Colitis, plays an important role in limiting specific inflammatory immune, fibroblasts and endothelial cells to facilitate intestinal epithelial stem cell recovery. By using a combination of latest sequencing technologies, they provide a tool for comprehensive analysis of the inter cellular networks of the colon in health, disease, and during treatment. Implementing these new single-cell and spatial technologies simultaneously in individual patients will lead to more precise treatment algorithms, and therefore a way for precision medicine.

Click on the link below to see the study


Gut bacteria break down cholesterol

In a new study, researchers found that gut bacteria can break down cholesterol. They identified  bacteria in the human gut that have an enzyme that can convert cholesterol into a form that isn't absorbed by the body. The study supports previous work indicating a link between bacterial enzymes that can modify cholesterol. This research could potentially be used to develop probiotic-type treatments to replace or support traditional treatments for managing cholesterol, like statins.

For a summary of the research, click here

For the whole research paper, click here

Blog image credit:  Susanna Hamilton, Broad Communications

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