Date of Award

Spring 2020

Degree Name

Master of Medical Science (Physician Assistant)

Department

Physician Assistant; College of Health Sciences

First Advisor

Michael L Huber, MMS, PA-C, DFAAPA

Abstract

Abstract

Introduction: Prostate cancer is the leading cancer affecting men of all races in the United States, and the second leading cause of cancer death in men. If caught early, many have had success in combating the disease, but if the cancer metastasizes, the 5-year survival rate drops to only 30%. Current treatment options heavily involve hormone therapy, radiation therapy, chemotherapy, and surgery. While these treatments can be effective for early stage prostate cancer, they can fall short in preventing the spread of the cancer to other parts of the body. This review analyzes a new potential way of preventing metastasis of pancreatic cancer by discussing the clinical question: In men 60 and older with prostate cancer (P), does manipulation of alternative splicing, through modulation of spliceosomes of Androgen Receptor Splice Variants (AR-Vs)(I), result in better preventing the patient’s cancer from becoming resistant and metastasizing(O), when compared to standard therapeutic treatments(C)?

Methods: A literature search was conducted through PubMed, Academic Search Ultimate and Google Scholar in November of 2018. A total of seven articles consisting of controlled clinical trials involving AR-Vs were selected, based on their relevance to the research question, study design, outcome measurements, and results.

Results: Based on the literature in this study, AR-V7 has a significant directly correlated link to metastatic prostate cancer. Four studies show that AR-V7s are seen at higher concentrations in CRPC cells and that they can be linked to the reason why many current hormone therapies are not effective in managing prostate cancer from spreading. Three studies show that by modifying AR-V7s with productive splicing, there was significant CRPC cell death. Overall, six different studies showed the potential for medication to suppress AR-V7 in prostate cancer treatment leading to favorable health outcomes going forward.

Discussion: The majority of studies found to have significant positive results when it comes to the presence of AR-V7 and inhibition of the splice variant with novel medications. A limitation was that the outcome measurements differed between each study, not allowing for one conclusive factor to be measured between them all. The studies lack long term outcomes and data on any potential adverse effects of the new medications. Also, the majority of studies involved using cells in a laboratory setting and not with alive human patients. Thus, there is a need for future studies to determine if AR-V7 modulation can be a long-term effective treatment in combating CRPC.

Conclusion: Castrate Resistant Prostate Cancer leads to current treatments using hormone therapy or radiation therapy being unable to effectively treat the cancer. These studies show AR-V7 to be present at high levels within these cells and that current hormone therapy is ineffective against it. Multiple novel medications inhibiting AR-V7 have shown to decreased the amount of active AR-V7 in those cells, leading to CRCP cell death. These studies did not look at the long-term effects of these medications on a larger number of human Prostate Cancer patients, leading to the need for future studies in this area.

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Manipulation of AR-V7 in Castrate Resistant Prostate Cancer

Abstract

Introduction: Prostate cancer is the leading cancer affecting men of all races in the United States, and the second leading cause of cancer death in men. If caught early, many have had success in combating the disease, but if the cancer metastasizes, the 5-year survival rate drops to only 30%. Current treatment options heavily involve hormone therapy, radiation therapy, chemotherapy, and surgery. While these treatments can be effective for early stage prostate cancer, they can fall short in preventing the spread of the cancer to other parts of the body. This review analyzes a new potential way of preventing metastasis of pancreatic cancer by discussing the clinical question: In men 60 and older with prostate cancer (P), does manipulation of alternative splicing, through modulation of spliceosomes of Androgen Receptor Splice Variants (AR-Vs)(I), result in better preventing the patient’s cancer from becoming resistant and metastasizing(O), when compared to standard therapeutic treatments(C)?

Methods: A literature search was conducted through PubMed, Academic Search Ultimate and Google Scholar in November of 2018. A total of seven articles consisting of controlled clinical trials involving AR-Vs were selected, based on their relevance to the research question, study design, outcome measurements, and results.

Results: Based on the literature in this study, AR-V7 has a significant directly correlated link to metastatic prostate cancer. Four studies show that AR-V7s are seen at higher concentrations in CRPC cells and that they can be linked to the reason why many current hormone therapies are not effective in managing prostate cancer from spreading. Three studies show that by modifying AR-V7s with productive splicing, there was significant CRPC cell death. Overall, six different studies showed the potential for medication to suppress AR-V7 in prostate cancer treatment leading to favorable health outcomes going forward.

Discussion: The majority of studies found to have significant positive results when it comes to the presence of AR-V7 and inhibition of the splice variant with novel medications. A limitation was that the outcome measurements differed between each study, not allowing for one conclusive factor to be measured between them all. The studies lack long term outcomes and data on any potential adverse effects of the new medications. Also, the majority of studies involved using cells in a laboratory setting and not with alive human patients. Thus, there is a need for future studies to determine if AR-V7 modulation can be a long-term effective treatment in combating CRPC.

Conclusion: Castrate Resistant Prostate Cancer leads to current treatments using hormone therapy or radiation therapy being unable to effectively treat the cancer. These studies show AR-V7 to be present at high levels within these cells and that current hormone therapy is ineffective against it. Multiple novel medications inhibiting AR-V7 have shown to decreased the amount of active AR-V7 in those cells, leading to CRCP cell death. These studies did not look at the long-term effects of these medications on a larger number of human Prostate Cancer patients, leading to the need for future studies in this area.