Sunday, November 24, 2013

Better Drugs

CUTAG of the Week:


The p53 protein has been long-established as a tumor supressor protein and pharmaceuticals continue to accommodate its role in cancer in many of their drugs.  How do you think the present study’s findings will most likely affect future drug development?  What strategies would you choose to pursue as the most effective in addressing the p21/PUMA ratio discussed?

58 comments:

  1. As is always the case in biomedical research, new discoveries are constantly being made that affect treatment plans for patients. In this case, additional information to the long known p53 involvement in cancer will in my opinion change cancer treatment courses for patients. Now, with the finding that the p21 to PUMA ratio is also important in tumor suppression, I think drug companies will be racing to develop drugs that promote favorable PUMA to p21 ratios, while ensuring that appropriate p53 levels are maintained. I still think it will be a long time until these drugs actually reach the market though, as the side effects of tampering with these protein ratios is not yet known. As Espinosa stated, though you may want one effect, you may end up with many other unwanted ones as well. Determining what side effects result from newly developed will require more research and time. The time it takes a drug to actually reach the market from development to prescription is a very long period. Nonetheless, this discovery will spark competition between drug companies to develop the most effective drug first.

    In terms of the p21/ PUMA ratio, I would of course want to first read the original article to gain a better background regarding how these ratios affect tumor development. Tipping protein ratios and interfering with them is a very delicate issue, as slight differences can cause the body to react in unexpected ways. Thus, I would say more research needs to be conducted to determine what these secondary effects would be. However, the information in this article regarding combining p53 and PUMA/p21 knowledge to create better cancer treatments looks promising.

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  2. This article is particularly interesting and applicable to class discussions because it hints at a possible genetic component linking levels of p21 and PUMA. Although the article does not directly address pharmacogenomics, I think the development of a drug that controls the p21/PUMA ratio would definitely require research into the genetic factors that determine p21/PUMA levels. As many of our readings have suggested, pharmacogenomics is the future of drug development. Personalizing medications to reduce adverse drug effects is becoming more and more critical to lowering healthcare costs and improving health outcomes.

    To further pursue this research into the p21/PUMA ratio, I would want to determine how the p21/PUMA ratio physiologically affects the p53 protein, thereby down-regulating it. I would then want to study the role of genetic variation in the expression of p53, p21, and PUMA. Using the identification of genetic variations, the p21/PUMA ratio could be altered and personalized in each distinct case. Therefore, each patient utilizing the p53 boosting drug could be tested and given a tailored treatment regime with a specific p21/PUMA ratio.

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  3. Elisabeth BellissimoNovember 25, 2013 at 10:59 AM

    How do you think the present study’s findings will most likely affect future drug development? What strategies would you choose to pursue as the most effective in addressing the p21/PUMA ratio discussed?

    I think that these findings will greatly affect the future of drug development because now that the p21/PUMA ratio has been found to be important for the effectiveness of tumor suppressing proteins and drugs, it will be beneficial for drug companies to produce drugs that cater to the balance as well as p53. This is extremely relevant to our recent classes focusing on pharmacogenomics and how it will be essential in the future of drug development.

    In order to address the effectiveness of the p21/PUMA ratio, I think that more research will need to be done to find out exactly how the ratio affects the p53 protein. Once this is discovered, it will become easier to develop drugs that directly aim to control the perfect balance of p21/PUMA while also activating p53. With pharmacogenomics becoming a much more prominent field in recent years, drugs have the opportunity to become a lot more effective while creating less side effects for patients and this will be essential to more personalized and productive treatment.

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  4. The discovery of the p21/PUMA ratio should drive many pharmaceutical companies to research and develop drugs that will create a favorable ratio. Along with the discovery of this ratio too companies should try to look at other ratio and variables in the genome to create more effective drugs. In addition to creating new drugs, pharmaceutical companies can start to create more specific target drugs tailored to individual genomic variants. However, this means that people will need to take more drugs to in order to make the main drug more effective. This could lead to more problems with toxicity among a plethora of other negative health effects that could arise with taking more drugs. For finding which drug is effective in addressing the ratio I would probably conduct research and then start clinical trials with patients.

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  5. I think this study is going to be a catalyst for future drugs that allow other drugs to be more effective. Specifically, drug companies will want to create a drug that creates good p21/PUMA ratios. However, this is tricky because any drug can have adverse side effects. And even though a second drug may help the original drug, it may also block other drugs from working. Obviously, more research must be done to insure that these drugs are safe and effective.

    As I said before, more research must be done on the p21/PUMA ratio. Researchers could test how the drug acts on other genetic variations. It would also be beneficial to see how this ratio specifically affects the p53 protein. Hopefully, pharmacogenomics will become much more important in the medical field, allowing for personalized medicine. This study is an indicator that the medical field is heading towards that.

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  6. I believe that we are a long way from actually dispersing effective drugs with minimal side effects when fighting cancer. The discovery of having more PUMA than p21 killing tumors is extraordinary since scientists had figured out what correlation of proteins actually kill tumors. In figuring out the ratio what we know from the reading is that there must be a higher amount of PUMA than p21 and that is where scientists will probably focus their efforts on. However, one basic strategy to scientists can have to figuring out this ratio is creating personal drug dosages to a specific person. Another treatment method medical professionals can have is creating a universal dosage that won't harm a person and slowly increasing that dosage of the drug as the person build tolerance.

    A lot of these ideas will take time to implement and it is inevitable that these basic ideas are going to be implemented. There must be many trials and research before drugs get marketed and that is another issue medical professionals have to figure out before they can prescribe these kinds of drugs.

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  7. I think new information to p53 involvement could change cancer treatment for patients in a positive way. I think that drug companies are going to be rushing to be the first to develop the p21 to PUMA ratio is important to tumor suppression. Because of the slow nature of drug development, I think that it will take a long time to be able to get a drug that also has the appropriate p53 levels. Side effects of these proteins are unknown, but could be explored through pharmacogenomics. I think that it’s going to take a long time for this drug to even be close to done because of the problem of negative side effects, but it definitely will be something of the future.

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  8. This is an encouraging step to cancer treatment. Finding the optimal p21 to PUMA ratio is the most important goal here. However, it will take the drug company a long time before they can release it to the market if it manages to pass the testing phase. One of the reasons why drug development is costly and long is because drugs often trigger adverse side effects. Adverse side effects is the 6th leading cause of death in the US. The company also needs to be ensure that p21/PUMA ratio does not cause any unintended consequences in the host's body. Using 2 drugs may create new side effects or amplify existing adverse effects that may harm the human body. It will be a very long time before we reap the benefit of this study if there are any benefits at all.

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  9. I think this study's findings will positively affect cancer drug treatment. The link between the p21 and PUMA ratio is extremely essential in creating an effective drug to stop the growth of tumors. With this information I believe scientists will be able to tailor drugs to make the ratio optimal for stopping the growth of tumors. However, it's important to not overlook the fact that there is a lot more that goes into drug making than optimal outcomes. There needs to be in-depth studies to prove that a drug that effectively fixed the ratio would not cause significant adverse effects that outweighed the benefits of the drug.

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  10. These findings are promising for cancer drug development. This information will prove useful in creating drugs that are more effective and efficient at killing tumors. The p21/PUMA ration is a great find but I think there needs to be research into the other genes that effect tumor growth and cell death. Adverse outcome should be investigated further before we tout a new drug.

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  11. These findings provide a strong support for the need to develop efficient drugs for those suffering with diseases, such as cancer, as shown in this article. Creating drugs that "reactivate the tumor-suppressor gene p53" would be extremely beneficial in reducing tumor growth and consequently cancer, as the p53 protein turns off uncontrolled replication. However, whenever a gene or protein is influenced or manipulated, it can cause either positive or negative side effects, or even both. More research need to be conducted and tested in order to determine the effects of what happens when reactivation of the p53 gene occurs and how it impacts the rest of the cell cycle/other bodily functions. However, if these side effects can be discovered and then a drug created to not produce any risky (adverse) side effects would be very beneficial to cancer patients The article states that a second drug that would "target genes that control the p21/PUMA ratio, in order to make the first drug more effective". Studying how this ratio changes and is regulated among cancer and non-cancer patients may be an important method to evaluate the most effective way to ensure that a specific ratio is met. Overall, I think this research is very promising. But like the creation of all new drugs, thorough research must be conducted, trials must be run and tested, therefore, the creation of new drugs, (2 new drugs in this example) will not occur overnight.

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  12. This study is important because it incorporates the interaction of genes and drugs to suppress tumors which is promising since so much of the topic of cancer is not understood. This article shows the difficulty of such relationships of first learning what genes are involved with PUMA versus p21 production and then coming up with effective drugs to balance these genes. This kind of research will have great outcomes for drug development in the future because researchers will be able to create drugs that serve the effect that they want while reducing unintended side effects since you know what genes the drugs target. Since this research of the interaction of gene activation and drugs is fairly new, I am curious what more studies down the road will conclude to then be able to market drugs based on the findings.

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  13. The idea of cancer is so personal to so many people, because the horrible disease comes in many forms and still holds so many mysteries as to causes and prevention methods. It is comforting to know that we can use knowledge of genomics to battle cancer, but as we learned in class, making new drugs accessible to large amounts of people is a strenuous and expensive process. Creating more affordable ways to allow greater amounts of people to receive the benefits of new drugs is just as important as putting new drugs on the market. Perhaps in time we will be able to not only utilize our genomics in battling cancer, but also utilize our healthcare system efficiently in allowing everyone a chance to be well.

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  14. Synergy: The whole is greater than the sum of the parts. This article is just such an example. A disease as complex and variable as cancer will likely need to be treated with more than one drug as this article demonstrates. Genetic testing may provide the key to the right mixture of drugs to beat cancer.
    As for addressing the P21/PUMA ratio, perhaps a genome wide association study could yield additional data. It could unveil information about the genes that affect this ratio. Once those genes are identified, action can be taken to improve the ratio. This will be the job of cancer researchers.

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  15. This article really drives home the importance of pharmacogenomics. This research shows that instead of just targeting one gene, multiple genes must be targeted for the best effects. I think this sheds light on what might be cause of other issues with drugs that are not effective in their treatments. In this case the p53 is a know tumor suppressor, but its effectiveness is determined by the PUMA/p21 ratio which is in turn is controlled by a handful of genes. I think this really goes to show that many genes may be underlying cause of the ineffectiveness of a drug therapy. To address this particular case, more research should be conducted. Furthermore, this case shows that more should be invested in pharmacogenomics.

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  16. I think these findings are fascinating and show a lot of prospect for the future of pharmacogenetics. As they still need to work on the development of a more tailored drug to stop tumor growth, I wonder if eventually they will go even further to create a preventative drug. With genetic screening for pre-phase biomarkers a specified drug that prevents tumors would be ideal for people who show future signs or ancestral history of cancer. Either way, with these new discoveries the future in cancer treatment is bright. To address the ratio I think more research needs to be done on a low risk population or test group to ensure all possible risks are eliminated. Whenever a drug is used in conjunction with another, it increases risk. Since this study suggests using a drug for tumor-suppressor gene p53 as well as a second drug targeting genes that control this p21/PUMA ratio, the risk is amplified and therefore more precautions would need to be taken.

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  17. I think that, more than anything else, this article really shows the importance of pharmacogenomics, as earlier mentioned above. I think that scientists and researchers are slowly learning that multiple genes need to be targeted in multiple ways in order to really have a beneficial impact on the patient. I also think it is becoming more and more evident that different people will have different reactions to the same drug due to other factors such as genetic variation and epigenetics. I think that all drugs like these ones should be more fine-tuned in order to benefit the patient. A more accurate ratio needs to be found to ward off tumor cells and I believe that this sort of meticulous fine-tuning on a person-to-person basis will be more common in the future.

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  18. The findings have opened up a brand new door to controlling different non-infectious diseases that are gene-linked. These diseases, which have been found to be linked to genes, can now be suppressed and almost eliminated thanks to the research found about the role of P53 and the ability of it's suppression when exposed to the tumor. By focusing on the ratio of p21/PUMA, the drugs will most likely help the drug that is reactivating p53 gene. As a result, more focus should go towards secondary drugs that can help the primary drugs as well as the individual. This secondary drug can help create a hostile environment for the tumor, however what comes to mind is the risk of the damages to the patient. Because there are more drugs required to treat the tumor, this may put a strain on the person's health and overall ability to overcome their cancer if they plan on doing chemotherapy as well. The overall findings can help with diseases such as heart disease, obesity, and other types of cancer. The overall research capabilities has been expanding at an exponential rate. Hopefully, soon, we can apply this knowledge and experience of research in other areas.

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  19. I think this has great potential to influence the drug industry and out overall health as a result of drugs in a great way. We do not know enough about the study design or other methods to be able to discern whether the results to this study alone would be enough to have evidence to advance pharmacology. I would be interested in knowing how these genes are being investigated, and if they are investigating the genetic sequence as a whole or individual genes and switches.
    I think the most effective strategy to investigate the p21/PUMA ratio as a result of different switches would be the most difficult one, which would be investigating each switch individually. The most effective strategy would be to turn on the switches that when activated increase the p21 the greatest, and turn off the switches that when turned on increase the PUMA concentration the most. Like someone stated above, there is an increased risk when taking multiple drugs at once, so we need to be vigilant if prescription drugs are how we would go about tipping the scales in the p21/PUMA ratio.

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  20. This study, in my opinion, is genomics at one of its finest moments. Cancer is a very tricky disease because of its growth in such a short period of time. It can create tumors and spread through different parts of the body easily. Because of this, the effectiveness of treatments are not always straightforward. I think that this study’s findings on the p 21/PUMA ratio and its effectiveness in the tumor suppressing gene p53 will greatly affect the future of drug development. Now researchers can have a specific target to focus on. Obviously it will take more time in research and development, but I think that this will revolutionize tumor treatments and therapies. I feel that they will be much more effective and possibly even quicker with this second drug that will alter the p21/PUMA ratio. These drugs have the potential to reduce side effects make the tumor treatments more effective. In addition, I think that more research in other drug development will focus on similar strategies. In the end, I think that research in this field will help to make existing drugs stronger. I think that another development that would come about with this study is to potentially make one drug that acted both as a tumor suppressant and had an effect on the p21/PUMA ratio. This way, it would be easier on the patient to take only one drug instead of multiple ones.

    I am not really one hundred percent sure as to what the best strategies would be best in addressing the ratio that was mentioned in the article. However, I know that there are important steps to take. First of all more research has to be done in this field. Genetic screening has helped the study come this far, and I think it is essential to continue using these screenings to understand how to address the p21/PUMA ratio issue. In the study, the researchers went in and turned offal the genes in the genome to see which ones would have the most effect in altering this ratio. I think that this is a good start since they found some potential genes involved in the ratio. Now I think that testing the suspected genes individually is required.

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  21. How do you think the present study’s findings will most likely affect future drug development?

    I believe that this study will pave the way for pharmaceutical companies to begin taking into account the concept that genes that do not directly affect the medical issue in question are still very important. For example, in this case, the p21/PUMA ratio affects the p53 gene, which in turn affects tumor growth. Therefore, studies like this will help identify the importance of acknowledging the interrelatedness of genes across the genome when developing drugs that work with our genetics.

    What strategies would you choose to pursue as the most effective in addressing the p21/PUMA ratio discussed?

    I believe that developing drugs that work together to control p53 and the p21/PUMA ratio will be the most effective strategy; clearly, drugs that only control the p21/PUMA ratio cannot stop tumor growth by themselves, and drugs that reactive p53 alone are not enough to stop tumor growth.

    Shanika Gilmour

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  22. These findings will open doors to the future drug development. Drug companies can use these new discoveries of the p21/PUMA ratio to develop tumor suppressing proteins and drugs. Researchers will also look into finding other ratio and variables to discover the different types of proteins that can turn off cancer. Pharmacogenomics can incorporate human genome into the research so that drug companies can make drug cater to each individual.

    I agree with the students above that a genome-wide study would be effective in addressing the P21/PUMA ratio. It could look at what specific genes that will affect the ratio.

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  23. I believe that these findings and future studies will be very key for future drug development and warding off possibly cancerous tumors. Drug companies can future study these associations and see how to turn off cancer cells. I think this will clearly be a hard thing to do and it will take a lot of time to figure out. Phrarmacogenomics may further complicate things especially if certain medications come from the findings that may harm or effect certain people. That being said, I do believe taking a risk like that is worth it if a possible off switch for some cancer cells can be found.

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  24. The findings in this article will pave the way for future drugs, especially those which target cancer, and those which work at the genetic level. There are many factors that affect tumors, such as the p21/PUMA relationship and their affect on p53 gene, and these findings of interrelatedness will open many doors in the future of drug development. I believe the most effective studies for the p21/PUMA ratio will involve turning off every gene in the human genome. Through this trial and error process, I believe that scientists will be able to discover an effective method to suppress tumors.

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  25. I believe that p53 is the future for cancer treatment. The association between p21 and PUMA is a large component of this cancer treatment, however, more research should be conducted to see if there are other ways to suppress tumors. The process of developing drugs is a very long and expensive process, so although p53 can play a huge role in cancer treatment, it is going to be years until we begin to see results. An important step in this process is to figure out what adverse side effects occur, and how to prevent those.

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  26. I think this study will greatly impact the future direction of drug development. It is important to understand that many drug therapies produce unnecessary side effects so it is great to see researchers discovering genes such as p21 and PUMA that can influence how effective the treatment is by finding the correct ratio. However, developing new drugs and therapies is extremely expensive and time consuming. As much as "personalized drug therapy" sounds appealing, I don't think it is the best course of action. I think combining more drugs could actually produce more side effects and adverse consequences, based on drug and gene interactions. There is still a lot we don't know, and I agree with other students that say the next step is to test the candidate genes individually.

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  27. While I’m sure that the processes described were vastly oversimplified, this research seems to have “immense promise” as the article puts it. At the very least, this leads to greater understanding of cancerous tissue and both pharmacogenetics and pharmacogenomics. At best, it leads to great specificity of efficacious, personalized treatment.

    I’m excited for the proposed next step of “repeating the genetic screen with additional tumor and healthy cell lines to discover which of their newly discovered candidate genes are common controllers of the p21/PUMA ratio across cancer types.” It looks to be an effective strategy that could find an exploitable root cause of many types of cancer. If such a finding exists and can be reached, then this diverse disease won’t be so diverse anymore. Nearly anyone with cancer would have a new, effective option to take. Barring toxicity, genomic-specific side effects, and access, the whole species can ascend to a higher level of treatment together.

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  28. As the article stated, killing off tumors by using drugs that turn on p53 will only kill off 1 in 10 tumors and the increase of p53 seems to cause an imbalance in the ratio of p21/PUMA. To prevent the decrease in PUMA, a drug should be made that gives cancer patients increased amounts of active p53 gene as well as PUMA. An alternative way is to have patients take the drug that turns on p53 in the body and have a drug p21 suppressor. However, this could also have side effects such as the inability to create new cells. The ratio between these regulatory factors is very sensitive and up regulating one can cause multiple side effects. The purposed solution is to work at a genomic level where we regulate the expression of the genes that promote the survival of PUMA.

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  29. I think that the present study’s findings will affect new drug development a great deal. Dr. Espinosa and his team have opened up a new window in the field of cancer research and consequently, introduced new issues that should be addressed. I am hesitant to endorse pursuing further research with these drugs, but feel that it may be an important step in winning the battle against cancer. I think the next logical step based on these findings is definitely to find the balance that maximizes the benefits and minimizes the risk of the p21/PUMA ratio. I think that the only way researchers can find this balance is trial and error, as goes with all experimentations. They have already found a couple dozen genes already involved in this p21/PUMA ratio, that most importantly lead to more cell death. To some degree, finding the perfect balance is a game of genetic roulette that may or may not be successful in the end in terms of effectively controlling tumor cells and possibly decreasing cancer prevalence overall. However, like the article stated, whether the ultimate turn out be positive or negative, learning how to manipulate the p21/PUMA ratio could offer a plethora of opportunities in the field. I don’t think giving more drugs is going to be the solution to anything. With the given possibility of adverse side effects, as Espinosa said, administering more drugs could be more detrimental to one’s health than beneficial.

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  30. This article brings up an important point in the search for new pharmaceuticals to combat the growing incidence of noncommunicable diseases. It shows that the fight to end diseases like cancer, diabetes, and cardiovascular disease is not as straightforward as we once thought. As many have noted previously, this article shows the increasing need for a pharmacogenomic lens in research laboratories and doctors' offices. If we want to reduce the DALYs from diseases like cancer we need to focus on the big picture rather than each individual gene. If we focus on one gene, such as p53, and ignore genes that code for PUMA, we are not going to get far in the push to reduce the effects of cancer. This article also points out the need for a greater communication among the science and medical communities. Without open communications and honest publishing it will be difficult to move forward.

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  31. I think these studies will have a large effect on the future of drug development. With these studies, pharmaceutical companies will be racing to see who can develop the better drug. I also think, however, that while this is a great discovery, the potential side effects need to be looked at. We would need to look at how drugs targeting p53 and the p21/PUMA ratio would affect not only the tumor, but all the other cells in our body.

    I think that in general to ward off tumors we should be looking more to preventative ways to avoid cancer overall, rather than using more drugs that could cause other side effects that could be detrimental to our health. I think Victoria was right in saying that, focusing on one gene will not make a huge difference of the effects of cancer and we need to be looking more at things that will have a larger effect.

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  32. As far as future drug development is concerned, I think that the study’s findings are a positive indication that new tumor suppressing drugs can be developed that take advantage of the newly discovered relationship between the p21 and PUMA proteins. While this is not necessarily true, there is a very good chance that the new information will help in the development of new treatments. I’m not entirely sure what strategy would be the most effective in addressing the p21/PUMA ratio, but I’m sure that it would involve devising a way to promote the production of one and not the other.

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  33. It is clear that activation of gene p53 turns off cancer, but simply turning on this gene is not enough to cause tumors to die. It has been found that tumors that die create more PUMA than p21. This study’s findings will likely influence researchers and pharmaceuticals to try to develop a drug targeting genes that control the p21/PUMA ratio, as these genes seem to “fine-tune this p53 effectiveness”. The study will likely lead to the development of drugs that will turn on genes that will cause tumors to create more PUMA than p21, subsequently leading to tumor death. Drugs targeting the p21/PUMA ratio will likely be more effective in killing tumors and ameliorating the effects of cancer than drugs that solely activate the p53 gene.

    Scientists involved in the study have already found a couple dozen genes involved in the p21/PUMA ratio. A strategy I would use to pursue in addressing the p21/PUMA ratio would be to screen these genes in an effort to show which of the genes regulate the “desired, tumor-killing response” and which lead to undesirable side effects. This would be done in an effort to make a more effective and safer drug.

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  34. I also believe that these p53 findings will greatly benefit the future for drug development. It is definitely going towards a good direction which may allow research for other tumor suppressing drugs. I think we should also look for other genes in addition to the p21/PUMA ratio. Although the activation of p53 turns of cancer, it doesn't kill off all the tumors. We can't just rely on these few genes.

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  35. This study shows promise in cancer research, but the present research does not seem to find a cure for cancer or the next best treatment when specifically targeting the p53 gene. When the p53 gene was targeted, only 1 in 10 tumors were actually killed, which shows a small effect. If technology and research can isolate why it only works sometimes and how to always replicate that, then this could be a viable solution in the pharmaceutical world. However, the question arises about how much money and resources would be needed to investigate this specific therapy, and if it's worth it- are there other treatments that may have better efficacy?

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  36. I believe this study’s findings will have a huge impact on future drug development. Like they mentioned, they might be able to make drugs that have the desired effect but not the undesired side effects. However, this type of drug development will be dependent on improved genome sequencing methods. Although paying attention to side effects will be beneficial I believe figuring out which of the “couple dozen genes involved” in the ratio of p21/PUMA is most influential in the ratio would be the most beneficial approach. If they are all equally influential then drug developers might be able to concentrate on one or two genes as opposed to multiple ones, which would be much more difficult.

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  37. The present study's findings will definitely help the future drug development. This will lead to a better understanding of cancer tissues and pharmacogenetics. However, more research on p53 protein is needed.A most effective strategy can be finding other genes rather than just relying on p21/PUMA ratio.

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  38. The p53 gene, is a tumor suppressor gene, its activity stops the formation of tumors. If a person inherits only one functional copy of the p53 gene from their parents, they are predisposed to cancer and usually develop tumors in a variety of tissues in early adulthood. However, mutations in p53 are found in most tumor types, and so contribute to the complex network of molecular events leading to tumor formation. The article states,the findings of the the p21 to PUMA ratio is very important in tumor suppression and therefore impact the developments of drugs in the future. Drug companies will develop drugs benefit the ratios of PUMA but also does not cause any unwanted side effects. The article also indicates the amount of information that exists on all aspects of p53 in human cancers is now vast, reflecting its key role in the pathogenesis of human cancers. However I would further study the role of genetic variation in the expression of p53, p21, and PUMA to understand the full scope of this problem.

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  39. I think this present study will cause future drug developers to allow for activation of the p53 protein more. As the article stated, the tumors with a PUMA:p21 ratio in which the PUMA proteins outnumbered the p21 proteins were the tumors that died. Therefore, I would say they should make drugs that can allow more PUMA than p21 into the tumors, therefore killing more tumors. However, since this is a new discovery, there are likely to be side effects to drugs that address the p21/PUMA ratio, therefore, the developers need to be careful on the population they use it on and how widespread they make these drugs before there are negative consequences that can be avoided.

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  40. I agree with previous students' comments that a genome-wide study would be effective in addressing the ratio. If drug developers can perfect this, great progress will be made in for future cancer treatment. As with just about everything, more research needs to be done to maximize benefits. This relates well to what we have been discussing in class about pharmacogenomics. It is also important to look further into why not all tumors died, and what can be done to target more tumors.

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  41. I think that this article just proves the importance of Pharmacogenomics. Spathe study found that the PUMA-p21 ratio is an important factor in determining cancer development along with the p53 gene--information that is totally new to us. With each new discovery, more and more questions open up, even if we don't realize which questions should have been asked until later on. Genetics is no simple thing. I think the existing p53-affecting drugs could be modified further as part of pharmacogenomics to make a favorable PUMA-p53 ratio catered to each persons DNA. Cancer is a complex disorder, and maybe we just can't treat it the same in everyone. As stated in the article, sometimes the p53 drugs work and sometimes they don't. Maybe it's genetics that determines those odds too. I think that more research has to be completed to see what is changing the PUMA-p21, but that this definitely supports the importance of pharmacogenomics.

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  42. I believe this study shows there is promising research being made in drug development and cancer research, however there is still no cure for cancer or effective treatment targeting the p53 gene. Only 1 in 10 tumors were actually killed when the p53 gene was targeted showing the gene has a small effect. I think the p21/PUMA ratio is a significant discovery but more research needs to be conducted to ensure its effectiveness and to look into other genes that effect tumor growth and apoptosis. Because the possible side effects for interfering with protein ratios are still unknown, more research must be conducted, meaning it will be awhile until this practice is in place. But discoveries like these indicate that we are making progress in cancer research and drug development, which is important in the hopes of one day finding a cure for cancer.

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  43. This article was very interesting. What I found very interesting was the ratio discussed in the article. The fact that the ratio can be measured in tumor cells of patients speaks to the accuracy and correctness of data in this research. This in turn can yield very promising and useful findings in terms of cancer research. The drug discussed seems to be more of a helper, like a secondary drug to aid in the primary drugs purpose. This can open up many avenues in medicine. We may be able to revisit older drugs once thought to be obsolete in today's day and age. Contemporary drugs can become more effective. In terms of the future, more opportunities have been open for effective cancer treatment drug regimens. So in terms of the effects of drug treatment programs and new drugs for cancer treatment, more research must be done. Although this research seems very promising, it still seems to be its infancy. By maintaining solid research and determination, better methods for cancer treatment can be found using this method.

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  44. With these findings, I believe this has open brand new dynamics of how cancer should be approached, in addition, shows there is promising potential. Ultimately since there is still a lack of innovation to combat cancer in the p53 gene, the wonders of a successful cure seams bleak but with more research of the p21/PUMA ratio seems like an ideal discovery for a looming vantage. The only problem, that seems to hinder this from to going into full effect seems to be the unknown insecurities of a new phenomenon. Nonetheless, further research must be done to figure why a few of the tumors died and why some lived. Hopefully this furthers cancer research and brings us that much closer to a cure.

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  45. There are always new innovative strategies being utilized to increase drug effectiveness. While at first they seem like a new-window of hope, they can often turn into problems in the future. For example, being able to use more of a drug due to their increased effectiveness seems to only increase resistance of tumor cells eventually. However, once further research is conducted it seems like there is a high potential that this new dynamic of approaching cancer will be effective. Altering the p21/PUMA ratio seems like a viable method.

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  46. Vanessa Merta

    I found this article very interesting. I did not know much about how genes effect cancer growth, so it was fascinating to learn about how the P53 gene is turned off and on. I think in future drug development, the P53 gene should be a huge focus. Though the scientists doing this research were able to pinpoint P53, only 1 in 10 tumors were actually stopped once the gene was turned back on. This showed that cancer was caused by more than one gene. If scientists were able to perfect this method of turning on and off genes then eliminating diseases like cancer would be an attainable goal. I think another research focus that should come out of this study would be the ability to differentiate between why something has side effects, and the genes that can turn off these side effects. Many drugs have extremely terrible side effects, including current cancer drugs. If we could isolate the effects and side effects of cancer drugs, then the patient fighting the cancer will be, in a way, healthier, and their body will be able to focus on fighting the cancer. I think that if we could eliminate side effects, we will be able to create much more effective drugs.

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  47. I think this article was interesting and enlightening to to find out the genomics behind cancer and how drugs that fight cancer work. I believe that this study will affect future drugs because it will continue the production of the drug that activates p53 with research that focuses on finding out in which circumstances the PUMA protein outnumber the p21 protein. I believe that pharmaceutical companies will invest in the research that helps to bring more information to light. I believe that I would use a slightly similar strategy suggested in the reading in order to address the issue of the p21/PUMA ratio. I would compare the genes of a person in which the P53 drug was effective to a genes of a person in which the p53 drug was ineffective or less effective. I would then compare the ratio p21/ PUMA protein ratios which would suggest that the patient in which p53 was effective had a higher ratio or PUMA than p21. This would also researchers to find out which genes are turned on or off and which ones affect the ratio of p21 to PUMA.

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  48. Finding more evidence that proves that the p53 gene is important towards cancer treatment could lead to some developments in the pharmaceutical industry. I think that the efforts will be on trying to make existing drugs more potent, but my opinion is that first the efforts should be on fine tuning the medicine and reducing side effects. With stronger drugs I feel like the bacteria and viruses will eventually adapt like they have in the past. By fine tuning the drugs first many of the discomforts that people have with side effects would be gone, and from there making the tumors disappear would already be easier because people would be able to be more active and have less pain and suffering in their lives.

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  49. This comment has been removed by the author.

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  50. Drug developers will most likely continue to investigate the effects drugs have on p21/PUMA ratio. Researchers will target secondary genes to help maximize the effects drugs have on tumor suppression. They will look into drugs that can supplement the activation of the p53 protein by increasing the number of PUMA proteins.

    I believe that cancer drugs should be given out as separate doses in a treatment plan. By giving patients separate doses, there is room for corrections. One dose will be given to minimize the direct problem, which will be the reactivation of p53. The next will be given to correct for side effects, such as the abundance of p21 proteins over PUMA proteins. By targeting p53 first, the protein can work to suppress some tumors before drugs are introduced to alter protein levels to combat the rest.

    Of course, more research has to be done before patients can receive these treatment plans. This research should look into the causes of change in p21/PUMA ratio, and how that connects to the reactivation of p53. As mentioned in the article, researchers should conduct more studies to figure out which genes cause p21 proteins to outnumber PUMA proteins.

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  51. How do you think the present study’s findings will most likely affect future drug development? What strategies would you choose to pursue as the most effective in addressing the p21/PUMA ratio discussed?

    I think this topic highlights how genomics is such a growing field in terms of drug development. Pharmacogenomics is a new field of developing medicine by using genetic screening create drugs that target certain genes that are responsible for different types of diseases or illnesses. In this example, researchers can develop a drug that targets specifically for the mutated p53 gene that is known for its cancer causing effect. By developing drugs that can reactivate this gene and prevent cancer would be an awesome defeat in medicine. Perhaps this can be passed on (epigenome) to future generations so that one day we can eliminate inherited cancers!

    However, like many of my peers mentioned, more research must be done before we start prescribing these sorts of treatments. More background research and studies needs to be done discover what genes are responsible for the p21/PUMA ratio and how that can be controlled. In any pharmacogenomics study, obtaining an evidence-based clinical study of these types of interventions are still something the field of genomics need to work on. Hopefully after overcoming this 'hump' we will be able to utilize the knowledge gained by both the pharmaceutical and genomics field.

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  52. The p53 protein has been long-established as a tumor supressor protein and pharmaceuticals continue to accommodate its role in cancer in many of their drugs. How do you think the present study’s findings will most likely affect future drug development? What strategies would you choose to pursue as the most effective in addressing the p21/PUMA ratio discussed?

    As the article mentioned, future drug development will lead to medicines with fewer side effects that can be used in higher doses to be more potent. It will hopefully lead to more specified drugs that can target the P21/Puma ratio better to effectively kill more tumors. Hopefully continuation of studies can lead to a drug that contains a protein more effective to kill the tumors with a higher P21 ratio so that scientists can combine drugs to kill tumors with high Puma ratio and tumors with high P21 ratio to kill a larger number of tumors over all. I would think that the most effective way to address the P21/Puma ratio problem would be to continue research to find a combination of proteins that will kill the most tumors with either type of ratio. (high p21 or high puma)

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  53. This article is very interesting to me in the sense that scientists are able to target specific genes that may have huge impacts on cancer. I believe that if more research is done with the p53 gene, there will be incredible amounts of development in the pharmaceutical industry. If techniques are made to permanently turn on the gene, this could be huge for cancer research. I always am skeptical at the beginning of research but I definitely think that in the future, the p53 gene and the p21/PUMA techniques will change the face of medicine.

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  54. I think this study will encourage future pharmaceutical drug developers to pursue P53 drug development. As the article stated, the tumors with a larger percentage of PUMA present as oppose to p21 proteins, were the tumors that died off. Furthermore the activation of p53 increases the amount of PUMA present and shifts the p21:PUMA ratio to a medically favorable proportion allowing for the death of tumor cells. In conclusion, drug companies should make drugs that activate these p53 proteins. As with all new discoveries, however, there will probably be negative side effects to drugs that take into consideration the p21/PUMA ratio.

    With that in mind pharmaceutical companies and drug creators should pay special attention to sensitive populations such as children and elderly. Special attention is needed here because, in these populations survival rates for cancer are usually lower than survival rates for cancer in populations ranging in the 20 - 50 age range.

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  55. This finding could help with forming future therapies that do not cause significant side effects. It gives something to researchers to work with. The hope is to give patients a drug to control the p21/PUMA ratio. Doing research on these three different things will help researchers and medical professional understand what combination ratio of these three are effective for what people. Will the same ratio be helpful for all people, or will it differ?

    I think what they stated in the article seems to be an effective way to address the p21/PUMA ratio. Trying to find out which of the newly discovered candidate genes have the most control over the p21/PUMA ratio seems to be the best bet right now. The only worry is what side effects could be created with molecularly targeted therapies.

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  56. This research will open a host of options to cancer patients that is not only less traumatic than chemo, but it may also be more cost-effective. When altering protein ratios, I'd be sure to review any pertinent literature on p21/PUMA ratios. Altering these ratios should be handled with the utmost caution, which is crucial in effective changes to these two interactions.

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  58. While there still needs to be a lot of research done in this field I think this study will increase the likelihood of finding a superior drug that boasts good p21/PUMA ratios. When we look at our pharmaceutical companies have fought to find the next big drug for so many years, it’s likely that they would put forth the time into this as well and really come up with the best drug possible. The safely of these drugs is very important. Much testing will need to be completed to determine their effects on humans, and in combination with other drugs.

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