Immunotherapy Drug for Advanced Lung Cancer

Lung cancer spreads to the brain in about one-quarter of patients with an advanced form of the disease. To date, radiation has been the only treatment option, but it comes with toxic side effects. Researchers at Yale Cancer Center (YCC) have found that use of the checkpoint inhibitor pembrolizumab in place of radiation can extend life with very few side effects in this patient population.

The findings, published in The Lancet Oncology, found that patient response depended on the level of the biomarker (PD-L1) expressed in their tumors. Of those that did respond, overall survival at one year was 40% and 34% at two years.

Pembrolizumab monoclonal antibody drug protein.

Survival in this cohort of patients exceeds the historically documented survival for patients with brain metastasis from non-small cell lung cancer or NSCLC, which is a two-year survival of about 14%,” said the study’s lead investigator Sarah B. Goldberg, M.D., M.P.H., associate professor of medicine (medical oncology) at YCC.

This is the first study to specifically test the benefit of the treatment in a prospective clinical trial of lung cancer patients who had not yet been treated for brain metastasis or whose tumors recurred after radiation. Before this, most clinical trials of a checkpoint immunotherapy drug did not include patients with brain metastasis, but the few that did provided hints of benefit when retrospectively analyzed.

Source: https://news.yale.edu/

Key Protein Behind Cancer Progression Can Be Reversed

Reports show that cancer is the second-highest leading cause of death globally, with the possibility that every one in four to five people in Singapore may develop cancer in their lifetime. A recent study by scientists from Duke-NUS Medical School provides new evidence supporting the presence of a key mechanism behind progression and relapse in cancer. The study, published in Proceedings of the National Academy of Sciences (PNAS), discusses the role of MBNL1 protein as a biomarker for cancer prognosis, which can lead to the development of new treatment strategies for cancer.

Cancer cases have been rising over the years and according to the statistics, the number of people living with cancer will continue to increase. Despite decades of research, cancer treatments are still inefficient and have unacceptable side effects that continue to prompt an urgent need for new approaches to prevention and treatment. Uncovering novel mechanisms associated with cancer would fill current knowledge gaps and help meet this need.

We discovered a mechanism involving MBNL1 protein that predicts several characteristics of cancer such as progression and relapse,” said Dr Debleena Ray, Senior Research Fellow at Duke-NUSCancer and Stem Cell Biology (CSCB) programme, the lead author of this study. ”We found that MBNL1 protein is present in low amounts in many of the common cancers in the world, including breast, colorectal, stomach, lung and prostate cancers, which when combined account for about 49 per cent of all cancers diagnosed in 2018. This can cause poor overall survival in many of these commonly-occurring cancers.”

The team also found that this mechanism can be reversed by blocking the JNK protein, a well-known target in cancer treatment, in cancer cells with low levels of MBNL1.

While JNK inhibitors have been tested as a cancer drug previously, currently there are no clinical trials for the same. However, if in the future there is a JNK inhibitor against cancer, MBNL1 could be used as a biomarker to select patients for the treatment,” said Adjunct Associate Professor David Epstein at the Duke-NUSCSCB programme and the co-corresponding author of this study.

Cancer is a global health challenge and Singapore is no exception. This study provides important information about novel targets and biomarkers that are implicated in several major cancers, which could lead to the development of new treatment strategies that can improve the lives of patients,” said Prof Patrick Casey, Senior Vice Dean for Research at Duke-NUS.

Over the next year, the team will be investigating the role of MBNL1 in colorectal cancer and exploring the potential of anti-JNK therapeutic for cancer using antisense technology, a tool that is used for the inhibition of gene expression.

 

Reference: Debleena Ray, Yu Chye Yun, Muhammad Idris, Shanshan Cheng, Arnoud Boot, Tan Bee Huat Iain, Steven G. Rozen, Patrick Tan and David M. Epstein (2020). A tumor associated splice-isoform of MAP2K7 drives de- differentiation in MBNL1-low cancers via JNK activation. PNAS. Complete research paper available at this link: https://www.pnas.org/content/early/2020/06/25/2002499117

Source: Duke-NUS

 

How To Catch Aggressive Prostate Cancer Early

Two newly published studies are presenting novel diagnostic techniques to help catch the most aggressive forms of prostate cancer at an early stage. A University of East Anglia study presents an innovative way to measure gene expression in tumor samples and predict disease severity, while an Australian study details a new kind of imaging technique promising to detect metastasized prostate cancer with greater accuracy than ever before.

Two new techniques are designed to detect aggressive forms of prostate cancer and catch it when it metastasizes

Prostate cancer is the most common cancer in men in the UK,” explains Colin Cooper, lead researcher on a new study from the University of East Anglia. “It usually develops slowly and the majority of cancers will not require treatment in a man’s lifetime. However, doctors struggle to predict which tumors will become aggressive, making it hard to decide on treatment for many men.”

In order to develop a way for doctors to better identify the most aggressive tumors the researchers examined different gene expression patterns in nearly 2,000 prostate tumor samples. Applying a mathematical model called Latent Process Decomposition, the study homed in on a particular pattern of gene expression associated with the most aggressive clinical cases.

The pattern relates to a subtype of cells the team has labeled DESNT, and suggest the more tumor cells in a sample that are of that DESNT subtype, the faster a patient will progress through the disease. The hope is that this can act as a biomarker to stratify prostate cancer patients, identifying those needing more urgent invasive treatments.

If you have a tumor that is majority DESNT you are more likely to get metastatic disease, in other words it is more likely to spread to other parts of your body,” says Daniel Brewer, co-lead researcher on the project. “This is a much better indication of aggressive disease.”

Identifying when prostate cancer has metastasized is obviously of vital importance in guiding treatment. A team of Australian researchers just published the results of a clinical trial evaluating the efficacy of a new imaging technique developed to provide detailed data on the spread of the disease.

Around one in three prostate cancer patients will experience a disease relapse after surgery or radiotherapy,” says Declan Murphy, senior author on the new imaging study. “This is partly because current medical imaging techniques often fail to detect when the cancer has spread, which means some men are not given the additional treatments they need.”

Source: https://newatlas.com/

Simple Urine Test To Spot Cancer

A Japanese firm is poised to carry out what it hailed as the world’s first experiment to test for cancer using urine samples, which would greatly facilitate screening for the deadly disease. Engineering and IT conglomerate Hitachi developed the basic technology to detect breast or colon cancer from two years ago. It will now begin testing the method using some 250 urine samples, to see if samples at are suitable for analysis, Hitachi spokesman Chiharu Odaira told AFP.

If this method is put to practical use, it will be a lot easier for people to get a cancer test, as there will be no need to go to a medical organisation for a ,” he said. It is also intended to be used to detect paediatric cancers.

That will be especially beneficial in testing for ” who are often afraid of needles,” added Odaira. Research published earlier this year demonstrated that a new blood test has shown promise towards detecting eight different kinds of tumours before they spread elsewhere in the body.

Usual diagnostic methods for breast cancer consist of a mammogram followed by a biopsy if a risk is detected. For , screening is generally conducted via a stool test and a colonoscopy for patients at high risk. The Hitachi technology centres around detecting waste materials inside urine samples that act as a “biomarker“—a naturally occurring substance by which a particular disease can be identified, the company said in a statement.

The procedure aims to improve the early detection of cancer, saving lives and reducing the medical and social cost to the country, Odaira explained.

The experiment is now completed in cooperation with Nagoya University in central Japan. “We aim to put the technology in use in the 2020s, although this depends on various things such as getting approval from the authorities,” Odaira said.

Source: https://medicalxpress.com/

Early-Stage Detection Of Alzheimer’s In The Blood

Two major studies with promising antibodies have recently failed – possibly because they have been administered too late. A new very early-detection test gives rise to hope. Using current techniques, Alzheimer’s disease, the most frequent cause of dementia, can only be detected once the typical plaques have formed in the brain. At this point, therapy seems no longer possible. However, the first changes caused by Alzheimer’s take place on the protein level up to 20 years sooner. A two-tier method developed at Ruhr-Universität Bochum (RUB) can help detect the disease at a much earlier stage. The researchers from Bochum published their report in the March 2019 edition of the journal “Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring”.

This has paved the way for early-stage therapy approaches, where the as yet inefficient drugs on which we had pinned our hopes may prove effective,” says Professor Klaus Gerwert from the Department of Biophysics at RUB.

In Alzheimer’s patients, the amyloid beta protein folds incorrectly due to pathological changes long before the first symptoms occur. A team of researchers headed by Klaus Gerwert successfully diagnosed this misfolding using a simple blood test; as a result, the disease can be detected approximately eight years before the first clinical symptoms occur. The test wasn’t suitable for clinical applications however: it did detect 71 per cent of Alzheimer’s cases in symptomless stages, but at the same time provided false positive diagnoses for nine per cent of the study participants. In order to increase the number of correctly identified Alzheimer’s cases and to reduce the number of false positive diagnoses, the researchers poured a lot of time and effort into optimising the test.

As a result, they have now introduced the two-tier diagnostic method. To this end, they use the original blood test to identify high-risk individuals. Subsequently, they add a dementia-specific biomarker, namely tau protein, to run further tests with those test participants whose Alzheimer’s diagnosis was positive in the first step. If both biomarkers show a positive result, there is a high likelihood of Alzheimer’s disease. “Through the combination of both analyses, 87 of 100 Alzheimer’s patients were correctly identified in our study,” summarises Klaus Gerwert. “And we reduced the number of false positive diagnoses in healthy subjects to 3 of 100. The second analysis is carried out in cerebrospinal fluid that is extracted from the spinal cord.

Now, new clinical studies with test participants in very early stages of the disease can be launched,” points out Gerwert. He is hoping that the existing therapeutic antibodies will still have an effect. “Recently, two major promising studies have failed, especially Crenezumab and Aducanumab – not least because it had probably already been too late by the time therapy was taken up. The new test opens up a new therapy window.”

Source: https://news.rub.de/

New Cheap Test Boosts Detection Of Diseases

Researchers at Queen’s University Belfast have developed a highly innovative new enzyme biomarker test that has the potential to indicate diseases and bacterial contamination saving time, money and possibly lives. The test, developed by scientists at the Institute for Global Food Security at Queen’s, can detect enzyme markers of disease known as proteases in humans, animals and food products.

Proteases are crucial for microorganism growth and are responsible for the progression of many diseasesLevels of proteases can be highly elevated in the urine of patients with diabetic kidney disease, or at the sites of infected wounds. Similarly, in cows, an elevation of proteases in their milk can reveal diseases such as bovine mastitis, a type of mammary gland infection. In food, proteases produced by bacteria contaminated in meat and dairy products can lead to rancidity, as well as decreased shelf life and quality. Current protease detection methods are costly, time-consuming and are not always effective. Scientists at Queen’s Institute for Global Food Security have developed a nanosensor which has resulted in sensitive, fast and cost effective protease detection in milk and urine.

Not only is the test cheap to produce, but it can be used anywhere and is not reliant on laboratory conditions. Eliminating the need to carry out tests in a laboratory setting is life-changing. As well as being cost-effective, it means faster diagnosis,” says Dr Claire McVey, Queen’s researcher and co-author on the study.

The gold-nanoparticle based nanosensor devised by Queen’s researchers indicates when proteases are present through a visible colour-change reactionGold nanoparticles are well known for their capability in speeding up the oxidization of a chemical called tetramethylbenzidine (TMB), visible through a vivid blue-colour formation.

When we add TMB to the casein-covered gold nanoparticles, we can tell virtually instantly if proteases are present by whether or not the solution turns blue. Normally such testing takes much longer,” explains Dr Cuong Cao, the lead academic on the study.

Using this approach, proteases can be detected within 90 minutes without the need for complicated or expensive laboratory equipment.

The findings have been published in the journal Nano Research,

Source: https://www.qub.ac.uk/