Specific epigenetic pathway found to be involved in the development of melanoma drug resistance

RAS mutations are one of the most common cancer-causing genetic mutations, and the drug is now being studied in several cancer types. I think it's going to work especially well in tumors that are primarily RAS driven, including colon cancer and lung cancer. It might also work in other cancer types in combination with drugs targeting other genetic mutations, but further research is needed.

Data-driven models, such as Quantitative Structure Activity Relationships (QSAR), are incredibly attractive because they offer rapid methods for predicting molecular properties, including those that are difficult to access through fundamental chemical and physical theory. For new molecules, in related regions of chemical space to the training data, they can often be very accurate. The challenge is that they typically do not generalize across large diverse chemical and biological spaces. Therefore real care is needed when applying them to novel chemistry or biology. Some attempts to build more widely applicable QSAR models have been made in recent years, but most models in use today are still built for specific chemistries and properties owing to the scale and complexity of chemical space. When I started this work, especially for solubility predictions, the datasets were modest by today’s standards, often hundreds to a few thousand molecules. One of the first things that teaches you is to explore the data carefully, assess its quality and quantity, and only then move forward with modeling. The aim is to capture genuine relationships between numerical molecular descriptions and important target endpoints, but those relationships may be only locally generalizable. I also think the phrase “simple descriptors” is interesting. Some are simple, such as atom counts or bond counts, but others rely on detailed parameterization, group contributions, and graph-theoretical techniques. We still see these descriptors used today, sometimes alongside embeddings from graph neural networks or language models. The main lesson for me is that there is no single workflow. Each dataset, model, and end-use case needs careful thought.

More specifically, the study showed that the female patient produced very few cathelicidins, which is a natural toxin found in the immune cells of the lungs needed to fight tuberculosis. In most people infected by tuberculosis, tuberculosis bacteria attack the immune cells of the lungs. The immune cells fight the bacteria by eating them. But the tuberculosis bacterium has developed various evasive mechanisms that reduce the immune cells’ ability to digest and thus to kill the Mtb. “You could say that the tuberculosis bacterium has developed a way to lull the immune cells to sleep. This enables the disease the hide inside the immune cells, making it invisible to other parts of the immune system,” Martin Kongsbak-Wismann explains. This is where vitamin D enters the picture. Because vitamin D is able to counteract the soporific effect of the tuberculosis bacteria by making the immune cells produce more of the cathelicidin toxin. “Cathelicidin is like a microscopic needle that is able to pierce the tuberculosis bacteria. And when it does, it weakens the bacteria’s soporific effect on the immune cells. This restores the immune cells’ ability to kill tuberculosis bacteria,” says Martin Kongsbak-Wismann and adds: “We were amazed by the effect of vitamin D. In immune cells from healthy control subjects, vitamin D improved the cells’ ability to fight Mtb, whereas in the female patient’s immune cells we saw no response to vitamin D. This shows that vitamin D is key to the immune system’s ability to fight Mtb and prevent tuberculosis.” Al-Jaberi, F.A.H., et al. (2022) Reduced vitamin D-induced cathelicidin production and killing of Mycobacterium tuberculosis in macrophages from a patient with a non-functional vitamin D receptor: A case report. Frontiers in Immunology. doi.org/10.3389/fimmu.2022.1038960.

With the current drug discovery paradigm, it takes up to 15 years to translate an idea, such as hypothesizing a certain protein is important in a disease and testing this with targeting the protein with a drug, all the way through to proof of concept. The drug has to be filed with the regulatory authorities, having done all the safety and efficacy testing. It's a long process and it's also very costly. Estimates vary, but it's currently reckoned to cost over 1 billion dollars per drug. That’s partly because you have to pay for all the drugs that didn't make it. By the time you've taken a protein target and you've made a whole load of molecules that affect that target in the way you want them to, you've probably already spent a couple of years on it and then you have to take the best molecule through the appropriate safety testing in animals before proceeding to phase 1 testing in people. Even if you get to phase 1 testing, where you are just giving it to human volunteers for the first time, not even patients, about 95% of the compounds at the stage then fail to make it all the way through to the market. So, you’ve only got a 5% success rate. The odds are not good and, essentially, it is why so many companies have had to merge because, over time, this is becoming less and less sustainable as a business model.

Algae are photosynthetic aquatic creatures that grow through the consumption of nutrients, light, and carbon dioxide. They are a diverse group of creatures that include tiny single-celled algae and enormous kelp, as well as seaweed 1. Numerous prokaryotic and eukaryotic algae species are desirable food sources for humans due to their inherent qualities 2,3. Human intake of macroalgae such as seaweed and microalgae like phytoplankton dates back many years. Multicellular macroscopic aquatic plants, or macroalgae, are classified into three taxa: Phaeophyceae, or brown algae, Rhodophyta or red algae, and Chlorophyta or green algae. Microalgae, the unicellular counterpart of macroalgae, are categorized in a broader framework that includes prokaryotic cyanobacteria (blue-green algae), Euglenophyta, and Chlorophyta, which are genetically distinct from one another. The ancient populations of Chad and the Aztec culture were already familiar with the cyanobacteria spirulina, which is currently advertised as a superfood in the West 4. In Burma, Vietnam, and India, other cyanobacteria/microalgae, like Spirogyra and Oedogonium, were eaten as food or as a supplement 4. Seaweed is a staple of daily meals in many Asian and Pacific civilizations, including Korea, Japan, and Indonesia, as well as Hawaii and New Zealand 5.