Cancer
New combination therapy approach for metastatic ovarian cancer

A new approach to treating ovarian cancer has been discovered that, in preclinical laboratory testing, shrinks tumours and improves survival rates while simultaneously making tumours more receptive to chemotherapy treatment.
Ovarian cancer is the deadliest gynaecological cancer; patients with metastatic ovarian cancer have a 30 per cent chance of surviving for five years after their diagnosis.
The danger of metastasis (when cancer spreads throughout the body) is exacerbated in ovarian cancer for two main reasons. Firstly, ovarian cancer is naturally resistant to chemotherapy, so its presence anywhere is difficult to combat. Secondly, ovarian cancer tends to metastasize through peritoneal fluid into the peritoneal cavity that’s the larger space in the body that houses the stomach and intestines.
Cancer in the peritoneal cavity is especially dangerous because the area is naturally immunosuppressive and limits the body’s response to any tumours.
To combat the challenge of ovarian cancer, a research team turned to a possible solution from nearly a century ago.
In the late 1800s & early 1900s, New York surgeon William B. Coley achieved a cure rate greater than 10 per cent for some cancers by injecting patients with dead pathogens. Scientists later reasoned that this anti-cancer effect was the result of the immune system’s activation of myeloid cells which are the plentiful cells in the peritoneal cavity that when activated can mount a cancer-killing response.
Building on this concept, the team designed an approach that specifically activates myeloid cells within the peritoneal cavity through combination treatment with β-glucan, a pathogen-derived activator of myeloid cells, and interferon-gamma (IFNγ). Preliminary reports suggest the approach can work to reverse immunosuppression around tumors.
“This is the first time researchers have been able to indirectly target ovarian cancer cells in peritoneal fluid by inducing an immune reaction, in preclinical models,” said The Wistar Institute’s Nan Zhang.
“We look forward to taking this research further — particularly our findings on the role of IL27 — so we can continue to identify other strategies to improve this new anti-ovarian-cancer approach.”
Their findings confirmed that this combination therapy worked when tested in preclinical lab models. After treating metastatic ovarian cancer models with both β-glucan and IFNγ, total tumour burden shrank substantially relative to controls. This disease reversal was consistent even in chemotherapy-resistant strains of ovarian cancer, which the team also modelled.
“Our work has opened the door to a possible new method of treating a particularly aggressive cancer,” said Brennah Murphy, Ph.D., first author of the paper.
“Ovarian cancer is infamous for resisting treatment, but we’ve shown — at the preclinical level — our treatment overcomes that resistance.”
Menopause
Cancer drug could tackle osteoporosis menopause weight gain

An experimental cancer drug reduced bone loss and body fat in mice modelling post-menopausal changes, early research suggests.
The compound, CADD522, appeared to strengthen bones and help the animals stay leaner after surgery designed to mimic hormonal changes seen after menopause.
The treatment remains at an early experimental stage and has so far only been tested in animals.
The study, led by the University of East Anglia, investigated CADD522, which was originally developed to block a protein involved in the growth and spread of several cancers.
Mice treated with the compound for eight weeks showed significant improvements in bone health. Scans found increased bone volume and better preservation of the honeycomb-like structures inside bones that are crucial for strength and resilience.
Blood tests suggested the treatment stimulated new bone growth without interfering with the body’s normal process of breaking down and rebuilding bone.
Dr Darrell Green, lead researcher from UEA’s Norwich Medical School, said: “Osteoporosis affects around one in three women over the age of 50, leaving sufferers vulnerable to painful fractures that can seriously impact quality of life.
“Current treatments exist, but many are plagued by side effects, safety concerns or inconvenient dosing schedules that make long-term use difficult.”
The researchers also found that mice receiving CADD522 weighed less than untreated mice despite eating the same amount of food.
They had less body fat and fewer fat deposits in their bone marrow, a process commonly seen after menopause and linked to declining bone health.
The team also examined brain tissue and found that the drug appeared to reverse several menopause-related changes in fatty acids.
Levels of omega-3 fats including DHA remained largely intact, while several other lipid abnormalities shifted back towards healthier patterns.
Green said: “We didn’t directly test for memory or thinking ability, but our work raises questions about whether this drug could one day help address wider menopause-related health problems.”
Safety experiments in mice, rats and dogs found that CADD522 could be taken orally and was well tolerated.
The compound also appeared to be metabolised more slowly in human tissue than in rodents, potentially improving its performance in people.
“This is still in the early stages and has so far only been tested in animals but we hope that the benefits will translate to humans to ultimately reduce fracture rates,” added Green.
The research was led by UEA in collaboration with the University of Maryland, the Scintillon Research Institute in San Diego and the University of Stirling.
Safety testing was funded by The Sir William Coxen Trust as part of the development of CADD522 as a childhood cancer treatment.
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