scholarly journals Strategies for Optimizing the Clinical Impact of Immunotherapeutic Agents Such as Sipuleucel-T in Prostate Cancer

2012 ◽  
Vol 10 (12) ◽  
pp. 1505-1512 ◽  
Author(s):  
Ravi A. Madan ◽  
Thomas Schwaab ◽  
James L. Gulley
Keyword(s):  
Prostate Cancer ◽  
Immune Responses ◽  
Standard Of Care ◽  
Clinical Impact ◽  
Castration Resistant Prostate Cancer ◽  
Therapeutic Vaccines ◽  
Therapeutic Cancer Vaccine ◽  
Castration Resistant ◽  
New Strategies

Sipuleucel-T is a therapeutic cancer vaccine that has shown improved survival in men with metastatic castration-resistant prostate cancer. As a first-in-class agent, it has been met with both fan-fare and controversy. A broad review of immune-based therapies may reveal the delayed clinical impact of sipuleucel-T to be a class effect. As new strategies of immune-based therapy are developed, their effects can be optimized through better understanding of how they affect disease differently from more standard therapeutics. Furthermore, combination therapy with agents that can either work synergistically with immune-activating therapies or deplete immune-regulating cells may result in more vigorous immune responses and improved clinical outcomes. In addition, therapeutic vaccines may be ideal candidates to safely combine with standard-of-care therapies because of their nonoverlapping toxicity profile. The ultimate role of immunotherapy may not be to supplant standard therapies, but rather to work in concert with them to maximize clinical benefit for patients.

AR Copy Number and AR Signaling-directed Therapies in Castrationresistant Prostate Cancer

2018 ◽  
Vol 18 (9) ◽  
pp. 869-876
Author(s):  
Samanta Salvi ◽  
Vincenza Conteduca ◽  
Cristian Lolli ◽  
Sara Testoni ◽  
Valentina Casadio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Copy Number ◽  
Clinical Trial Design ◽  
Complete Information ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Anti Cancer ◽  
Hormone Sensitive ◽  
Predictive And Prognostic Biomarker

Background: Adaptive upregulation of Androgen Receptor (AR) is the most common event involved in the progression from hormone sensitive to Castration-Resistant Prostate Cancer (CRPC). AR signaling remains the main target of new AR signalling-directed therapies such as abiraterone and enzalutamide in CRPC patients. Objective: In this review, we discuss general mechanisms of resistance to AR-targeted therapies, with a focus on the role of AR Copy Number (CN). We reported methods and clinical applications of AR CN evaluation in tissue and liquid biopsy, thus to have a complete information regarding its role as predictive and prognostic biomarker. Conclusion: Outcomes of CRPC patients are reported to be highly variable as the consequence of tumor heterogeneity. AR CN could contribute to patient selection and tumor monitoring in CRPC treated with new anti-cancer treatment as abiraterone and enzalutamide. Further studies to investigate AR CN effect to these agents and its potential combination with other prognostic or predictive clinical factors are necessary in the context of harmonized clinical trial design.

scholarly journals Interplay Between SOX9, Wnt/β-Catenin and Androgen Receptor Signaling in Castration-Resistant Prostate Cancer

2019 ◽  
Vol 20 (9) ◽  
pp. 2066 ◽  
Author(s):  
Namrata Khurana ◽  
Suresh C. Sikka
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Signaling Pathways ◽  
Critical Role ◽  
Castration Resistant Prostate Cancer ◽  
Form Complex ◽  
Androgen Receptor Signaling ◽  
Castration Resistant ◽  
Signaling Axis

Androgen receptor (AR) signaling plays a key role not only in the initiation of prostate cancer (PCa) but also in its transition to aggressive and invasive castration-resistant prostate cancer (CRPC). However, the crosstalk of AR with other signaling pathways contributes significantly to the emergence and growth of CRPC. Wnt/β-catenin signaling facilitates ductal morphogenesis in fetal prostate and its anomalous expression has been linked with PCa. β-catenin has also been reported to form complex with AR and thus augment AR signaling in PCa. The transcription factor SOX9 has been shown to be the driving force of aggressive and invasive PCa cells and regulate AR expression in PCa cells. Furthermore, SOX9 has also been shown to propel PCa by the reactivation of Wnt/β-catenin signaling. In this review, we discuss the critical role of SOX9/AR/Wnt/β-catenin signaling axis in the development and progression of CRPC. The phytochemicals like sulforaphane and curcumin that can concurrently target SOX9, AR and Wnt/β-catenin signaling pathways in PCa may thus be beneficial in the chemoprevention of PCa.

The role of abiraterone in the management of metastatic castration-resistant prostate cancer

2012 ◽  
Vol 12 (4) ◽  
pp. 429-437 ◽  
Author(s):  
Alex Rawlinson ◽  
Aza Mohammed ◽  
John Beatty ◽  
Richard Bell ◽  
Marek Miller
Keyword(s):  
Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

New Strategies for Medical Management of Castration-Resistant Prostate Cancer

Oncology ◽  
2011 ◽  
Vol 80 (1-2) ◽  
pp. 1-11 ◽  
Author(s):  
Irène Asmane ◽  
Jocelyn Céraline ◽  
Brigitte Duclos ◽  
Lynn Rob ◽  
Valère Litique ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Medical Management ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
New Strategies

scholarly journals IL-7 expands lymphocyte populations and enhances immune responses to sipuleucel-T in patients with metastatic castration-resistant prostate cancer (mCRPC)

2021 ◽  
Vol 9 (8) ◽  
pp. e002903
Author(s):  
Russell K Pachynski ◽  
Chihiro Morishima ◽  
Russell Szmulewitz ◽  
Lauren Harshman ◽  
Leonard Appleman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cell ◽  
Immune Responses ◽  
Nk Cells ◽  
Observation Group ◽  
Castration Resistant Prostate Cancer ◽  
Activation Markers ◽  
Castration Resistant ◽  
Ifn Γ ◽  
Over Time

BackgroundSipuleucel-T (sip-T) is a Food and Drug Administration (FDA)-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). We hypothesized that combining sip-T with interleukin (IL)-7, a homeostatic cytokine that enhances both B and T cell development and proliferation, would augment and prolong antigen-specific immune responses against both PA2024 (the immunogen for sip-T) and prostatic acid phosphatase (PAP).MethodsFifty-four patients with mCRPC treated with sip-T were subsequently enrolled and randomized 1:1 into observation (n=26) or IL-7 (n=28) arms of a phase II clinical trial (NCT01881867). Recombinant human (rh) IL-7 (CYT107) was given weekly×4. Immune responses were evaluated using flow cytometry, mass cytometry (CyTOF), interferon (IFN)-γ ELISpot, 3H-thymidine incorporation, and ELISA.ResultsTreatment with rhIL-7 was well tolerated. For the rhIL-7-treated, but not observation group, statistically significant lymphocyte subset expansion was found, with 2.3–2.6-fold increases in CD4+T, CD8+T, and CD56bright NK cells at week 6 compared with baseline. No significant differences in PA2024 or PAP-specific T cell responses measured by IFN-γ ELISpot assay were found between rhIL-7 and observation groups. However, antigen-specific T cell proliferative responses and humoral IgG and IgG/IgM responses significantly increased over time in the rhIL-7-treated group only. CyTOF analyses revealed pleiotropic effects of rhIL-7 on lymphocyte subsets, including increases in CD137 and intracellular IL-2 and IFN-γ expression. While not powered to detect clinical outcomes, we found that 31% of patients in the rhIL-7 group had prostate specific antigen (PSA) doubling times of >6 months, compared with 14% in the observation group.ConclusionsTreatment with rhIL-7 led to a significant expansion of CD4+ and CD8+ T cells, and CD56bright natural killer (NK) cells compared with observation after treatment with sip-T. The rhIL-7 treatment also led to improved antigen-specific humoral and T cell proliferative responses over time as well as to increased expression of activation markers and beneficial cytokines. This is the first study to evaluate the use of rhIL-7 after sip-T in patients with mCRPC and demonstrates encouraging results for combination approaches to augment beneficial immune responses.

Clinical impact of detecting low-frequency variants in cell-free DNA on treatment of castration-resistant prostate cancer

2021 ◽  
pp. clincanres.2328.2021
Author(s):  
Kei Mizuno ◽  
Takayuki Sumiyoshi ◽  
Takatsugu Okegawa ◽  
Naoki Terada ◽  
Satoshi Ishitoya ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Low Frequency ◽  
Clinical Impact ◽  
Castration Resistant Prostate Cancer ◽  
Cell Free Dna ◽  
Castration Resistant ◽  
Free Dna
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