Preserving maternal RNA transmitted by an oocyte to its progeny is an essential aspect of oogenesis, yet not much is known about how this is achieved in mammalian species. In a recent issue of Science, researchers at the Max Planck Institute in Gottingen, Germany [Cheng et al. (2022)] uncovered the MARDO, a novel structure that may help answer this longstanding question.
The tumour microenvironment (TME) is a dynamic, highly heterogeneous structure consisting of both transformed (mutated) cells, non-transformed cells (including immune cells, stromal cells and blood vessels) and microbes. These cells are held in an extracellular matrix of proteins and other factors secreted by the cells. An increased understanding of the TME is behind many of the latest advancements in cancer therapy.
The goal of precision medicine is to understand the factors that contribute to the variability in the pharmacokinetics and pharmacodynamics of the drugs. It is now clear that the gut microbiome plays a critical role in the markedly different responses of individuals to identical drug therapy.
Great strides have been made in recent years in treating some cancers, such as melanoma. But despite huge efforts, little progress has been made in improving the odds for pancreatic ductal adenocarcinoma (PDAC). 95% of individuals receiving a diagnosis of PDAC survive less than 18 months. It is the worst prognosis of any cancer, making it set to be the second biggest cause of cancer mortality by 2030. Why is PDAC so difficult to treat and what strategies are being developed?
Just a decade ago, for the millions of people living with rare genetic diseases, there seemed little hope that an effective treatment could be developed. One of the main obstacles is the massive costs of drug development; for many rare genetic diseases, there aren't even enough patients to conduct a formal clinical trial. But changes to the regulatory framework and the development of gene therapy platform technologies that, once proven safe, may be rapidly turned to a wide number of disparate diseases, is offering hope.
Immunomodulatory drugs, such as Immune-checkpoint inhibitors (ICIs) have transformed cancer care. However, as with other cancer drugs, ICIs are associated with significant adverse events which can even be fatal. How do these occur and what is being done to reduce their severity?
Since the 1986 approval of Muromonab, the first therapeutic monoclonal antibody (mAb), used to treat steroid-resistant transplant patients, mAbs have rapidly evolved and gained clinical ground become the largest class of biopharmaceuticals. During this period, mAbs have garnered a reputation for safety, favourable PKPD, and high levels of specificity that have made them a preferred drug modality in many therapeutic applications.
Antimicrobial resistance (AMR) is on the rise. By 2050, AMR may be killing more people than cancer does now. Already, the mortality rates and economic impact are alarming. According to the Centre for Disease Control the total cost of AMR in the USA is estimated at $55bn and results in over 35,000 deaths each year. The worldwide death toll is ticking over 700,000.
Little more than 10 years ago, the prospects for gene therapy were bleak. Early clinical trials had served to highlight the risks. In particular, the 1999 death of Jesse Gelsinger proved a turning point, and clinical progress stalled for years. The risks are now better understood and controlled, and in recent years so much has changed. The FDA's 2017 approval of the first human gene therapy drug, Luxurna, heralded a new era with a further twenty gene therapies approved by 2019 with 1000 more in clinical trials.
Each year, 1.27 million deaths are caused by drug-resistant microbes. These bugs are currently developing resistance at a faster rate than new drugs are developed. In 30 years’ time, if this innovation gap continues, 10 million people are forecast to die each year from infections that were once treatable. Such a toll would surpass even cancer as a cause of mortality. With such a grave threat to human health, why isn’t more being done? Why aren’t more antibiotics being developed?
