Author: Calvin Inners
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 TMPRSS2–ERG fusion mutation and this mutation 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 has 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 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 and stored. Cancer cells impact how fats are broken down and used. 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 how 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.
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