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According to the World Health Organization, cancer is the second most leading cause of annual deaths worldwide. Its strong prevalence means that over 1,700,000 new cases are diagnosed each year in the US alone, with millions of people being treated globally at any given moment. A major area of cancer treatment is palliative treatment, which aims to relieve symptoms and side effects and to improve on quality of life. Chemotherapy, some targeted treatments, and radiotherapy commonly induce nausea and vomiting as a side-effect.
In addition, the cancer itself can cause these symptoms, through causing infections, blocking the intestine, interfering with the body’s usual mineral levels or by spreading to the brain. Currently, a range antiemetic drugs are available to help reduce these side effects, however, these drugs have limitations, and not all patients respond to them. The specific impact and interactions these drugs have on the body has not been fully understood. Experts were not able to gain a full comprehension of how they impact the body, and for this reason, it has proven difficult to improve on their effectiveness.
Importance of Electron Microscopy
Fortunately, new studies utilizing electron microscopy have been able to throw some light on the function of antiemetics. The most common therapeutic target for nausea management in cancer patients is the serotonin receptor (5-HT3AR). Setron is a form of antiemetic that targets serotonin receptors, classed as competitive antagonists they inhibit 5-HT3AR in the gastrointestinal tract and brainstem. Setrons are generally well-tolerated, but for some patients with cancer who experiencing vomiting later on in their treatment setron is ineffective. Until now the specific setron-receptor interactions that are key to reducing nausea have been unknown. But recent studies have been able to model the setron-receptor interactions, meaning that we can begin to understand how to improve them.
Just last year, a paper was published in Nature Communications elucidating the complete structure of the serotonin receptor, followed by 2 studies this year which have extended this investigation, looking into the interaction of setron with serotonin receptors in detail. The significance of which is discussed below.
Electron microscopy can obtain high-resolution images of biological samples, through the use of electrons as a source of illuminating radiation, as electrons have short wavelengths. In a recent study, researchers cooled samples to extremely low temperatures and studied them with the electron microscope. The images that were generated gave the ability to track the receptor-drug interactions with precise accuracy, movements of less than a billionth of a meter were picked up on. As a result, setron was viewed using the serotonin’s attachment site on the receptor, but using a slightly different pose, causing minor changes to the receptor’s shape. Now it is confirmed that the drugs utilizes this particular binding site, scientists can construct a more accurate model on the molecular workings of setron.
Experts have also been able to investigate setron’s most stable interactions with serotonin receptors and specific drug and receptor portions that are key for a secure connection were identified. With the knowledge of which are the most significant interactions between the drug and the receptor, and which orientation is most efficient in the binding pocket, scientists can understand how to improve the function of setron. Development can now take guided direction, opening the possibility of enhancing setron’s therapeutic effectivity.
Cancer treatment will be able to be improved by developing setron that is more effective at alleviating nausea and vomiting, thereby reducing the side effects of chemotherapy, radiotherapy, and other treatments. With the possibility of minimizing this common side-effect for a wider range of patients, treatment of cancer becomes less aggressive, more manageable for those going through it, and enhances quality of life.
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