Understanding Prostate Cancer

Prostate cancer is one of the most common types of cancer for men in the world. In fact, only lung cancer, breast cancer, and colorectal cancer affect more people. With this being said, one out of seven cancer diagnoses in men is due to prostate cancer. It is clear to say that the 3.1 million new prostate cancer diagnoses and 307,000 deaths a year due to prostate cancer is a significant problem for society.

One key step to solving the problem of prostate cancer is to understand what causes prostate cancer and how to classify the disease. Researchers have been able to determine four different mechanism that lead to tumorigenesis in prostate cells. One of which is the TMPRSS2ERG fusion mutation which accounts for almost 50 percent of the prostate cancer.

The TMPRSS2-ERG fusion mutation is a mutation to the TMPRSS2 and ERG genes. Two mechanisms can happen that can cause this fusion. First, the genetic information between TMPRSS2 and ERG is deleted therefore the two genes are right next to each other and become fused. Secondly, the TMPRSS2 gene can be translocated or essentially moved from its normal location on the chromosome to right next to the ERG gene. This fusion causes the genes to be continuously turned on. This increased activity of the gene causes the prostate cancer cells to grow uncontrollably leading to the symptoms of prostate cancer and the upregulation of different proteins. Luckily, these proteins can be analyzed to determine the prognosis of the prostate cancer.

In 1979, the field of diagnosing prostate cancer started to change. Dr. Michael Wang from the University of Chicago was the first one to purify a protein linked to prostate cancer known as Prostate Specific Antigen (PSA). This protein was isolated and purified since it was thought to be in higher concentrations when patients got prostate cancer. Through the 80’s and 90’s scientists confirmed the result found in the Wang lab and built upon his work to develop a test used in the clinic. Even though it was thought that PSA was the holy grail for prostate cancer diagnoses, scientists reevaluated this paradigm with new experiments. Scientists were able to determine that other techniques such as ultrasound and digital rectal exams in tandem with PSA diagnostics serves as the best  diagnosing practice for prostate cancer. Lastly, scientist have been trying to piece together why PSA is increased when a patient has prostate cancer and how this increase relates to other areas of prostate cancer, such as the TMPRSS2-ERG mutation and the PI3K pathway

The phosphoinositide 3 kinase (PI3K) pathway is responsible for the production of phosphatidylinositol-3,4,5-trisphosphate – a key component to cell survival, gene regulation, cell metabolism, and overall structure of the cell. Since there are many roles the PI3K pathway, many different proteins are responsible for signaling in this pathway. These proteins are known as kinases and each of theses kinases have a different target to regulate different functions in the pathway. Research in the past two decades has looked at what pathways the TMPRSS2-ERG mutation works through. Researchers found that the PI3K pathway is used to activate another pathway, AKT. Since AKT helps regulate processes similar to the PI3K pathway through phosphorylation or the adding of a phosphate group to proteins, it is important to ensure that this protein is properly regulated in terms of cell growth and replication – a common issue for cancer cells.

Until recently, the mechanism of how exactly prostate cancer works was unknown. Through the work of researchers, it was found that the prostate cancer cells impact the body as a whole, three different ways. Two of these ways impacts how fats are metabolized. The first of the two ways cancer cells impact metabolism is through how the prostate cells break down fats and use them. Additionally, these prostate cancer cells hijack the body’s source of resources and use it for their own nefarious purposes; mostly rapid growth and metastasis into other areas of the body. Lastly, the prostate cancer cells impact hormone signaling in the body; mainly testosterone. The prostate cancer cells control  the cellular mechanism for how cells recognize and import testosterone. With this improper hormone signaling, further issues can occur. These mechanisms are rather new to the scientific community and serve as an example of where the field is heading.

While there is a lot known about prostate cancer, there still is a lot that is left to be understood. One of the biggest issues facing patients with prostate cancer is diagnosing what mutation is present in the prostate cancer and treating the cancer cells based off these mutations. Additionally, it is important to understand how these different mutations affect prostate cancer cells. Lastly, more work needs to be done to better diagnose the disease since there have been some red flags raised around the PSA diagnostic tool.

 

For more Information about prostate cancer, visit my helpful blog!

 

For more general information about prostate cancer, click below!

http://cinners.bergbuilds.domains/about/introduction-to-erg-fusion-mutation-prostate-cancer/

For more information about the PSA assay, click below!

http://cinners.bergbuilds.domains/about/prostate-specific-antigen-2/

For more information about the TMPRSS2-ERG mutation, click below!

http://cinners.bergbuilds.domains/about/tmprss2-erg-fusion/

For more information about the PI3K Pathway, click below!

http://cinners.bergbuilds.domains/about/pi3k-pathway/

For more information about the disease mechanism, click below!

http://cinners.bergbuilds.domains/about/disease-mechanism/

For more information about where the field of prostate cancer is heading, click below!

http://cinners.bergbuilds.domains/about/further-work/

 

12 Comments

  1. Great information on prostate cancer. Now I know types of prostate cancer and how they affect the body , 3 different ways.

    1. That is a great question. Currently, there are some tests able to determine if there are mutations in the prostate cells. With this being said, cost is a major barrier for these tests being used in clinics and hospitals. For your age question, there is no research suggesting when to check for the mutations since there is not a standard protocol doctors follow to look for these mutations.

  2. Heartening to hear that there have been improvement in the medical community’s understanding of prostate cancer. Definitely more to learn!

  3. I don’t understand the hormone signaling. Prostate cancer cells disrupt how testosterone is recognized and imported, but what does that mean?

    1. Thank you for the great question, Caske! Basically, on each cell membrane there are a number of different receptors responsible for recognizing and transporting molecules from cell to cell. One can think of these receptors as mailboxes, and the molecules as mail. Basically what the prostate cancer cells does is change the mailboxes to different addresses so testosterone does not know where to go when entering or leaving the cell. These changes made to the cell can have drastic negative consequences and can lead to many other systems being dysregulated.

  4. Great information! I’m curious to know if the protate cancer is treated differently, once diagnosed, depending on which of these mechanisms caused it?

    1. Hey Christa, that is a great question! Currently, cancer treatments are not focused on the current mutations of cancer you have. They tend to focus more on where you have the cancer and the severity of the cancer. One possible future change to the way cancer will be treated is to pair the cancer drug to the specific type of mutation. Currently, a few studies have started to do this. So far, the scientists running these trials have seen some very promising results in certain cases. Thank you for reading my blog!

  5. Awesome read! What areas of the body are most common for prostate cancer cells to metastasize to? Also, what types of techniques are used to conduct this type of research?

    1. Hey Erin, thank you for taking the time to read my blog. While looking at the literature I saw a few articles suggesting that bones and lymph nodes were come places for utre metastasis of prostate cancer. For this set of research, I looked a variety of articles from biochemistry, cancer biology, epidemiology, and other health care related fields to find articles and I summed them up in this document. For the research done in the lab, a lot standard molecular biology techniques such as fluorescence microscopy techniques to analyze the cancer cells and molecular biology techniques were performed to look at the genes present in the prostate cancer cells.. I hoped this answered some of your questions.

  6. Calvin, very nice write-up. Since this fusion leads to a new protein, is there any indication that the immune system might recognize it as foreign and mount an immune response to this neoantigen ? Has anyone found T-cells infiltrated in prostate cancer tumors of patients who have spontaneous regression or very slow growing tumors ? If so, even if the immune response is not sufficient to stop the cancer, it might indicate that immunotherapy (Keytruda or similar drugs) might be an effective prostate cancer treatment. Also, one could make a vaccine to the TMPRSS2-ERG fusion protein. I believe there is a lot of interest in this approach right now. Check out this link
    http://blog.dana-farber.org/insight/2017/08/cancer-immunotherapy-taking-aim-with-neoantigens/

    1. Hey Jim, thank you for taking the time to read my article and leaving such great questions. While reading literature I did find many articles suggesting that the mutated protein was able to be destroyed by the immune system naturally. I would assume this is the case because the protein is just a combination of two proteins that are commonly seen in the body. Within the last 5 years or so groups have been trying to develop medicines and vaccines targeted at this specific mutation. One article (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864132/) I found interesting is from 2013 and talks about developing a peptide based vaccine to target the mutation. Additionally, this group uses T-cells to try and target the mutated protein – similar to an immunotherapy. I believe the end of your comment hit the nail on the head, there is a lot of interest growing in this field and I am excited to see how researchers solve this problem in the upcoming decades. Thanks again for reading my blog!

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