The Potential Future of Cancer Treatment
Proteins are an essential part of the body as they carry out most functions, such as metabolism and anabolism. However, like any machinery, they have to be dismantled and remade to ensure functionality and efficiency. This is where protein degraders come in. Humans use the ubiquitin-proteasome system, where proteins are tagged for destruction with tags called ubiquitin and then eaten by the proteasome. Certain protein degraders can harness this system to tag peptides involved in disease development for elimination, such as Proteolysis Targeting Chimera (PROTAC).
The typical cancer treatment involves small-molecule inhibitors, but protein degraders have a few advantages over this more traditional method. First, PROTAC can be used effectively in lower concentrations. Small-molecule inhibitors have to be given in high doses, which often lead to negative effects due to the drastic change the body is undergoing. Second, protein degraders can tag multiple copies of the desired protein for degradation. Lastly, they can also tag proteins that are not enzymes. This last advantage is distinctly important as pathogens that were not enzymes were thought to be impossible to remove via drugs due to the inhibitors needing a binding pocket on the target to be functional.
Additionally, protein degraders show activity against pathogens that are resistant to small-molecule inhibitors in patients who have already undergone the traditional therapy. Overall, this new medical technology appears more promising in theory due to its direct elimination of the target. As their name suggests, small-molecule inhibitors inhibit the pathogen, leaving them in the body. Fully destroying the disease is a more safe-proof method in case of future altercations.
The typical cancer treatment involves small-molecule inhibitors, but protein degraders have a few advantages over this more traditional method. First, PROTAC can be used effectively in lower concentrations. Small-molecule inhibitors have to be given in high doses, which often lead to negative effects due to the drastic change the body is undergoing. Second, protein degraders can tag multiple copies of the desired protein for degradation. Lastly, they can also tag proteins that are not enzymes. This last advantage is distinctly important as pathogens that were not enzymes were thought to be impossible to remove via drugs due to the inhibitors needing a binding pocket on the target to be functional.
Additionally, protein degraders show activity against pathogens that are resistant to small-molecule inhibitors in patients who have already undergone the traditional therapy. Overall, this new medical technology appears more promising in theory due to its direct elimination of the target. As their name suggests, small-molecule inhibitors inhibit the pathogen, leaving them in the body. Fully destroying the disease is a more safe-proof method in case of future altercations.
Each type of cancer tends to be caused by different proteins, which is why researchers have to design personalized protein degraders to treat every cancer. As seen above, proteins can be drastically different in size and shape, this is a monumental task.
Currently, protein degraders are in the very early stages of development with clinical testing starting in 2019. Results are beginning to emerge, and the notion that protein degraders could represent the future of cancer treatment is indeed promising. Key pathological peptides in prostate and breast cancer are the androgen and estrogen receptors, respectively. Two protein degraders were designed to destroy these receptors and in their clinical trials, the expression of these proteins decreased. Many kinks still have to be worked out, of course. Many patients who received this treatment in the trials claimed to have symptoms of vomiting, fatigue, diarrhea, and decreased appetite. These adverse cases were relatively mild; however, there is still room for improvement.
Further development however can lead to potential challenges. For instance, there is the concern of pathogens developing resistance to the protein degraders This is unknown due to the limited number and the small nature of the trials done so far, but it is a possibility. Additionally, every designed protein degrader has a limitation in that it has to be able to bind to the ubiquitin-proteasome system. Because of this, there might not be a protein degrader made for the pathogen of every type of cancer.
Overall, this new medical technology is very promising and research is being committed at an incredulous pace. The future of cancer treatment could be closer than you think.
Further development however can lead to potential challenges. For instance, there is the concern of pathogens developing resistance to the protein degraders This is unknown due to the limited number and the small nature of the trials done so far, but it is a possibility. Additionally, every designed protein degrader has a limitation in that it has to be able to bind to the ubiquitin-proteasome system. Because of this, there might not be a protein degrader made for the pathogen of every type of cancer.
Overall, this new medical technology is very promising and research is being committed at an incredulous pace. The future of cancer treatment could be closer than you think.
Featured Image Source: Chokniti Khongchum
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