Combining Androgen Deprivation and Immunotherapy in Prostate Cancer Treatment: A Mechanistic Approach
Due to its initial dependence on testosterone, prostate cancer patients are initially treated with androgen deprivation therapy, a form of chemical castration. However, in many cases, the cancer develops resistance to this treatment. Sipuleucel-T (Provenge), is the first live cell vaccine approved f...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Applied Sciences |
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| Online Access: | https://www.mdpi.com/2076-3417/12/14/6954 |
| _version_ | 1797407670532046848 |
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| author | Johnna Barnaby Harsh Vardhan Jain |
| author_facet | Johnna Barnaby Harsh Vardhan Jain |
| author_sort | Johnna Barnaby |
| collection | DOAJ |
| description | Due to its initial dependence on testosterone, prostate cancer patients are initially treated with androgen deprivation therapy, a form of chemical castration. However, in many cases, the cancer develops resistance to this treatment. Sipuleucel-T (Provenge), is the first live cell vaccine approved for treating patients with advanced, hormonally refractive prostate cancer. However, it has shown limited survival benefit. Recently, it has been proposed that combining Provenge with androgen deprivation may result in a better treatment outcome. Here, we develop a nonlinear dynamical systems model with a view to predicting the therapeutic potential of such a combination. Our model accounts for the mechanism of action of Provenge and the immune system response elicited by androgen deprivation. We use data from mouse xenograft experiments to calibrate and validate our model. The validated model is then used to explain the limited clinical success of Provenge, and predict optimal scheduling that maximizes the anti-tumor potential of Provenge combined with androgen deprivation. In particular, we demonstrate that the two treatments should be given concurrently, rather than sequentially, as is current practice. |
| first_indexed | 2024-03-09T03:45:57Z |
| format | Article |
| id | doaj.art-e0ac346988554ec881c3a3913f5b2500 |
| institution | Directory Open Access Journal |
| issn | 2076-3417 |
| language | English |
| last_indexed | 2024-03-09T03:45:57Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Applied Sciences |
| spelling | doaj.art-e0ac346988554ec881c3a3913f5b25002023-12-03T14:35:31ZengMDPI AGApplied Sciences2076-34172022-07-011214695410.3390/app12146954Combining Androgen Deprivation and Immunotherapy in Prostate Cancer Treatment: A Mechanistic ApproachJohnna Barnaby0Harsh Vardhan Jain1Department of Mathematics, Shippensburg University, 1871 Old Main, Shippensburg, PA 17257, USADepartment of Mathematics & Statistics, University of Minnesota Duluth, 140 Solon Campus Center, Duluth, MN 55812, USADue to its initial dependence on testosterone, prostate cancer patients are initially treated with androgen deprivation therapy, a form of chemical castration. However, in many cases, the cancer develops resistance to this treatment. Sipuleucel-T (Provenge), is the first live cell vaccine approved for treating patients with advanced, hormonally refractive prostate cancer. However, it has shown limited survival benefit. Recently, it has been proposed that combining Provenge with androgen deprivation may result in a better treatment outcome. Here, we develop a nonlinear dynamical systems model with a view to predicting the therapeutic potential of such a combination. Our model accounts for the mechanism of action of Provenge and the immune system response elicited by androgen deprivation. We use data from mouse xenograft experiments to calibrate and validate our model. The validated model is then used to explain the limited clinical success of Provenge, and predict optimal scheduling that maximizes the anti-tumor potential of Provenge combined with androgen deprivation. In particular, we demonstrate that the two treatments should be given concurrently, rather than sequentially, as is current practice.https://www.mdpi.com/2076-3417/12/14/6954ADTimmunotherapymathematical modelprostate cancerProvenge |
| spellingShingle | Johnna Barnaby Harsh Vardhan Jain Combining Androgen Deprivation and Immunotherapy in Prostate Cancer Treatment: A Mechanistic Approach Applied Sciences ADT immunotherapy mathematical model prostate cancer Provenge |
| title | Combining Androgen Deprivation and Immunotherapy in Prostate Cancer Treatment: A Mechanistic Approach |
| title_full | Combining Androgen Deprivation and Immunotherapy in Prostate Cancer Treatment: A Mechanistic Approach |
| title_fullStr | Combining Androgen Deprivation and Immunotherapy in Prostate Cancer Treatment: A Mechanistic Approach |
| title_full_unstemmed | Combining Androgen Deprivation and Immunotherapy in Prostate Cancer Treatment: A Mechanistic Approach |
| title_short | Combining Androgen Deprivation and Immunotherapy in Prostate Cancer Treatment: A Mechanistic Approach |
| title_sort | combining androgen deprivation and immunotherapy in prostate cancer treatment a mechanistic approach |
| topic | ADT immunotherapy mathematical model prostate cancer Provenge |
| url | https://www.mdpi.com/2076-3417/12/14/6954 |
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