News & numbers


“Given the almost infinite possibilities in which a tumour can evolve, and the very large number of cells in a late-stage tumour – which could be several hundred billion cells – achieving cures


in all patients with late-stage disease is a formidable task.” Professor Charles Swanton from the Francis Crick Institute and University College London


Hope for heart failure


A novel drug is showing promise for alleviating heart failure, a condition associated with sleep apnoea and a reduced lifespan. The drug was tested in an animal model at the University of Auckland, where researchers found it improved the heart’s ability to pump, but, equally importantly, prevented sleep apnoea, which itself has been proven in studies to reduce lifespan. “This drug does offer benefit for heart failure, but it’s two for the price of one, in that it’s also relieving the apnoea for which there is currently no drug, only CPAP (a breathing device), which is poorly tolerated,” said Professor Julian Paton, director of the University’s Manaaki Manawa Centre for Heart Research.


“This study has revealed the first drug to temper the nervous activity from the brain to the heart, thereby reversing the heart’s progressive decline in heart failure,” said Professor Paton.


“These findings have real potential for improving the wellness and life expectancy of almost 200,000 people living with heart disease in Aotearoa, New Zealand,” said Professor Paton. “Over recent decades there have been several classes of drugs that have improved the prognosis of heart failure,” added cardiology consultant and Associate Professor, Martin Stiles. “However, none of these drugs work in the way that this new agent does. So, it is exciting to see a novel method that potentially reverses some features of heart failure.”


Paradigm shift for prostate cancer


A new drug could improve the recurrence rate of cancer in patients that undergo surgery on the prostate to treat the disease, according to a recent study. In a phase 2 clinical trial, 32 men with high-risk or very high-risk prostate cancers who were scheduled for surgery were treated with six weekly infusions of enoblituzumab prior to their operations, and were followed for an average of 30 months thereafter. 21 patients, or 66%, had an undetectable prostate-specific antigen (PSA) level 12 months following surgery, suggesting that there was no sign of residual disease.


If enoblituzumab continues to perform well in further, larger randomised studies, it could represent a new pathway for immunotherapy against multiple cancers, and the first one that may have a role for prostate cancer, said lead study author Eugene Shenderov. “Enoblituzumab appears safe and seems to activate the immune system in a way that involves both T-cells and myeloid cells,” he said. “What this means is if these results can be replicated in a larger, randomised study, it opens the possibility that combining this therapy with local, curative-intent therapies like surgical prostate removal or radiation therapy,


Super-sized nanocages


Researchers from the University of Cambridge have built a super-sized nanocage. Nanocages are tiny artificial containers that can be used to deliver therapeutics to a target destination in the body, but some drug molecules are like gifts that are too big for a standard-sized nanocage ‘box’. Using a method inspired by natural biological systems, the Cambridge team were able to build progressively larger artificial nanocages, with the largest cage having an enclosed volume greater than 92nm3


– making it the largest ligand- 8


enclosed inner cavity volume ever made. Larger cages have been reported, but they have more open ligand frameworks, which are not as useful because these cages have not been able to bind cargoes. First author Dr Kai Wu, of the Yusuf Hamied Department of Chemistry, said: “The findings of this study are important because they demonstrate how we are able to create ever- larger complex, functional structures using simple building blocks.” The super-sized nanocages have potential applications in fields such as drug delivery


and biotechnology, where they could be used to deliver larger therapeutic biomolecules to specific parts of the body. The researchers also note that the large internal cavities of the nanocages could serve as a platform for the binding of large biomolecules, such as hydrophobic membrane proteins or proteases, which could be useful in drug discovery and development. Wu said: “Overall, this research expands our understanding of how to create nanoscale structures and may have practical implications in a variety of fields.”


World Pharmaceutical Frontiers / www.worldpharmaceuticals.net


would allow this drug to potentially kill micrometastatic disease hiding elsewhere in the body, and therefore prevent a significant number of men from experiencing recurring disease. That could be a paradigm shift in prostate cancer.”


The median age of study participants was 64 (age range 48–74). About half (47%) had a PSA greater than 10ng/ mL at diagnosis, which is abnormally high, and 50% had Gleason grade group 5 (1 to 5, the higher the grade, the greater the chance of recurrence) at biopsy, meaning they had highly aggressive forms of the disease. Side effects of enoblituzumab were generally mild and included fatigue, neurological symptoms such as headache or dizziness, and flu-like or cold symptoms. One patient developed inflammation of the heart (myocarditis), which fully resolved with steroid treatment and is a known side effect of other immune checkpoint drugs.


Investigators are now planning a larger, randomised trial of enoblituzumab in newly diagnosed prostate cancer patients to assess clinical activity of the drug compared to current standards of care.


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