This is an excellent question, as I’ve been thinking about this as well! I don’t know for sure, but here is my theorized thought process: Omeprazole and pantoprazole are both currently frequently used medications for various gastrointestinal problems; all it really dose within that area is decrease the amount of stomach acid that is produced, when excess acid is being produced. I’m not sure if it would be necessary to specifically target these cells with proton pump inhibitors because proton pumps are present in nearly every cell in the body (except red blood cells) so I would think that most proton pumps would be inhibited; the way that cancer cells would be targeted for death would be when using localized radiation, the cells that the radiation hits will most likely have a proton pump inhibitor, increasing the effects of that radiation within those cells. This is a really good question, and should be considered for future research involving these compounds!
Great question! We asked that same question once we saw our awesome results. If you look back at the poster at Figure D, you’ll see our results graphed; when serial dilutions were conducted for pantoprazole, the irradiated larvae with pantoprazole showed consistent results with our previous serial dilution of pantoprazole, however our non-irradiated larvae with pantoprazole showed a significantly higher survival rate of up to 80%! This large difference confirms our hypothesis that pantoprazole does in fact work synergistically with radiation by increasing the effects of radiation.
Yeah, great question! This is the coolest thing about these results, in my opinion! Cancerous cells consist of many mechanisms by which they avoid cell death, one being multi drug resistance, where cancer cells develop mutations that allow them to survive through whatever type of treatment is being used (chemotherapy, radiation therapy, etc.) and then pass those mutations on, resulting in relapse tumors. That’s why this experimental design specifically uses a combinatorial approach to cancer treatments so that if and when cancer cells develop such mutations, there is another kind of therapy there that the cancer cells have not become resistant to, thus eradicating the entire tumor. Therefore, the purpose of using radiation within this research is to combine radiation therapy with chemotherapy by identifying and using specific novel chemotherapeutic compounds that work synergistically with radiation, so that the effects of the radiation are increased by the chemotherapeutic compound without increasing the amount of radiation. This is huge because radiation not only kills cancer cells, but also healthy cells, so if we can increase the effectiveness of radiation without adding larger amounts of radiation that will harm the patient, cancer treatments may be more successful in terms of their survival rates; at the bare minimum, it make the treatment process somewhat easier for the patient.
Yeah! This research hasn’t been done before, so we weren’t 100% sure if these proton pump inhibitors would statistically identify as a “hit” (a potential chemotherapeutic compound). We hypothesized that both omeprazole and pantoprazole would work synergistically with radiation because of their mechanisms by which they would promote cell death through a decrease in intracellular pH to lethal levels. We were happy to see that both compounds showed synergistic and therapeutic effects; however, because this is the first time this has been done, we are not sure what about these proton pump inhibitors is allowing them to work synergistically with radiation/increase the effects of radiation. If I had to theorize why, I might suggest that maybe the proton pump inhibitors are also inhibiting radiation from being released from the cancer cell, increasing the amount of radiation within the cancer cell and thus increasing the effects of the radiation on the cancer cell.
How would Omeprazole and Pantoprazole specifically affect or be targeted to cancerous cells?
This is an excellent question, as I’ve been thinking about this as well! I don’t know for sure, but here is my theorized thought process: Omeprazole and pantoprazole are both currently frequently used medications for various gastrointestinal problems; all it really dose within that area is decrease the amount of stomach acid that is produced, when excess acid is being produced. I’m not sure if it would be necessary to specifically target these cells with proton pump inhibitors because proton pumps are present in nearly every cell in the body (except red blood cells) so I would think that most proton pumps would be inhibited; the way that cancer cells would be targeted for death would be when using localized radiation, the cells that the radiation hits will most likely have a proton pump inhibitor, increasing the effects of that radiation within those cells. This is a really good question, and should be considered for future research involving these compounds!
What would you expect the effects of your drugs to be when not paired with radiation?
Great question! We asked that same question once we saw our awesome results. If you look back at the poster at Figure D, you’ll see our results graphed; when serial dilutions were conducted for pantoprazole, the irradiated larvae with pantoprazole showed consistent results with our previous serial dilution of pantoprazole, however our non-irradiated larvae with pantoprazole showed a significantly higher survival rate of up to 80%! This large difference confirms our hypothesis that pantoprazole does in fact work synergistically with radiation by increasing the effects of radiation.
What was the point of radiation within this research?
Yeah, great question! This is the coolest thing about these results, in my opinion! Cancerous cells consist of many mechanisms by which they avoid cell death, one being multi drug resistance, where cancer cells develop mutations that allow them to survive through whatever type of treatment is being used (chemotherapy, radiation therapy, etc.) and then pass those mutations on, resulting in relapse tumors. That’s why this experimental design specifically uses a combinatorial approach to cancer treatments so that if and when cancer cells develop such mutations, there is another kind of therapy there that the cancer cells have not become resistant to, thus eradicating the entire tumor. Therefore, the purpose of using radiation within this research is to combine radiation therapy with chemotherapy by identifying and using specific novel chemotherapeutic compounds that work synergistically with radiation, so that the effects of the radiation are increased by the chemotherapeutic compound without increasing the amount of radiation. This is huge because radiation not only kills cancer cells, but also healthy cells, so if we can increase the effectiveness of radiation without adding larger amounts of radiation that will harm the patient, cancer treatments may be more successful in terms of their survival rates; at the bare minimum, it make the treatment process somewhat easier for the patient.
Can you further explain why radiation would cause the two proton pumps to work synergistically?
Yeah! This research hasn’t been done before, so we weren’t 100% sure if these proton pump inhibitors would statistically identify as a “hit” (a potential chemotherapeutic compound). We hypothesized that both omeprazole and pantoprazole would work synergistically with radiation because of their mechanisms by which they would promote cell death through a decrease in intracellular pH to lethal levels. We were happy to see that both compounds showed synergistic and therapeutic effects; however, because this is the first time this has been done, we are not sure what about these proton pump inhibitors is allowing them to work synergistically with radiation/increase the effects of radiation. If I had to theorize why, I might suggest that maybe the proton pump inhibitors are also inhibiting radiation from being released from the cancer cell, increasing the amount of radiation within the cancer cell and thus increasing the effects of the radiation on the cancer cell.
This is definitely something to consider for future research with these types of compounds!