scholarly journals Castration Resistant Prostate Cancer Research of Individualized Drug Therapy

2017 ◽  
Vol 07 (02) ◽  
pp. 123-129
Author(s):  
斌 郝
Keyword(s):  
Prostate Cancer ◽  
Cancer Research ◽  
Drug Therapy ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Individualized Drug Therapy ◽  
Prostate Cancer Research

Sex Hormones and Prostate Cancer

2020 ◽  
Vol 71 (1) ◽  
pp. 33-45 ◽  
Author(s):  
Richard J. Auchus ◽  
Nima Sharifi
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Current Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
History Of ◽  
Prostate Cancer Research ◽  
Prostate Cancers ◽  
Androgen Independent ◽  
Transition Studies

The prostate is an androgen-dependent organ that develops only in male mammals. Prostate cancer is the most common nonskin malignancy in men and the second leading cause of cancer deaths. Metastatic prostate cancer initially retains its androgen dependence, and androgen-deprivation therapy often leads to disease control; however, the cancer inevitably progresses despite treatment as castration-resistant prostate cancer, the lethal form of the disease. Although it was assumed that the cancer became androgen independent during this transition, studies over the last two decades have shown that these tumors evade treatment via mechanisms that augment acquisition of androgens from circulating precursors, increase sensitivity to androgens and androgen precursors, bypass the androgen receptor, or a combination of these mechanisms. This review summarizes the history of prostate cancer research leading to the contemporary view of androgen dependence for prostate cancers and the current treatment approaches based on this modern paradigm.

Drug therapy methods in patients with metastatic castration-resistant prostate cancer: Role of somatostatin analogues

2017 ◽  
Vol 6 (3) ◽  
pp. 76
Author(s):  
A. A. Krasheninnikov ◽  
K. M. Nyushko ◽  
E. Yu. Safronova ◽  
A. S. Kalpinsky ◽  
A. A. Kostin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Therapy ◽  
Somatostatin Analogues ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals 582 Immune correlates from QuEST1 in men with castration-resistant prostate cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A612-A612
Author(s):  
Nicole Toney ◽  
Yo-Ting Tsai ◽  
Jason Redman ◽  
James Gulley ◽  
Jeffrey Schlom ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Research ◽  
T Cells ◽  
Clinical Response ◽  
National Cancer Institute ◽  
Checkpoint Inhibitors ◽  
Castration Resistant Prostate Cancer ◽  
Immune Correlates ◽  
Immune Parameters ◽  
Castration Resistant

BackgroundImmune checkpoint inhibitors have limited efficacy in unselected metastatic castration-resistant prostate cancer (mCRPC) patients. Combination immunotherapy approaches to generate a tumor-directed immune response (vaccine) and facilitate the resulting anti-tumor immune activity (checkpoint inhibitors, cytokines) have shown synergy preclinically. In the phase I/II Quick Efficacy Seeking Trial (QuEST1, NCT03493945), combination of a brachyury-targeting vaccine (BN-brachyury), TGF-β/anti-PD-L1 blocking bifunctional fusion protein (bintrafusp alfa), and IL-15 superagonist (N-803) have produced preliminary evidence of efficacy in CRPC, with 5/12 patients having a sustained prostate-specific antigen (PSA) response that included 2 radiographic partial responses, compared to 1/13 patients who received BN-brachyury plus bintrafusp alfa. Here, we present immune correlates from patients enrolled in Arm 2.1A (BN-brachyury + bintrafusp alfa) and Arm 2.2A (BN-brachyury + bintrafusp alfa + N-803).MethodsPeripheral blood mononuclear cells (PBMC) and serum were obtained from 25 patients pre and multiple time points post treatment. PBMCs were assessed for antigen specific T cells targeting brachyury and MUC-1 by intracellular cytokine staining, 158 peripheral immune cell subsets by multicolor flow cytometry, and TCRVβ sequencing. Patients were also evaluated for complete blood counts, and serum cytokines/soluble factors using ELISA assays and OLINK’s immuno-oncology panel. Immune parameters were compared between Arm 2.1A and Arm 2.2A and evaluated for associations with clinical response in Arm 2.2A.ResultsBrachyury and MUC-1 specific T cells were increased in most patients post treatment in both arms. A greater increase in total NK cells, refined NK subsets expressing markers of activation/adhesion, and TCR diversity was observed after 2 weeks of therapy in Arm 2.2A than Arm 2.1A. Absolute lymphocyte counts and serum levels of granzyme B, sCD27, and sCD40L were also increased after 2 weeks in Arm 2.2A compared to Arm 2.1A. Serum proteomic analyses revealed a greater increase in analytes related to NK cell signaling in Arm 2.2A than Arm 2.1A. Specific immune parameters at baseline associated with development of clinical response in patients treated in Arm 2.2A; responders had trends of higher frequencies of CD4+ and CD8+ T cells, lower frequencies of MDSCs and monocytes, and lower levels of serum IL-6 and sCD40 than non-responders.ConclusionsThese findings demonstrate enhanced immune activation of both NK and T cells with the addition of N-803 in Arm 2.2A, where more clinical activity was observed than in Arm 2.1A. These findings support the continued evaluation of the combination of BN-brachyury, bintrafusp alfa, and N-803 in patients with mCRPC.AcknowledgementsThis research was supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health, and via Cooperative Research and Development Agreements (CRADAs) between the NCI and EMD Serono, the NCI and Bavarian Nordic, and the NCI and ImmunityBio.Trial RegistrationNCT03493945Ethics ApprovalThe trial was approved by the Institutional Review Board of the Center for Cancer Research, National Cancer Institute (ClinicalTrials.gov identifier: NCT03493945).

scholarly journals Current Status of Castration-Resistant Prostate Cancer Drug Therapy

2021 ◽  
Vol 6 (1) ◽  
pp. 41-49
Author(s):  
Yifeng Mao ◽  
Mingqiu Hu ◽  
Gaowei Yang ◽  
Erke Gao ◽  
Wenbang Chen
Keyword(s):  
Prostate Cancer ◽  
Drug Therapy ◽  
Current Status ◽  
Cancer Drug ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

New combination therapies for castration-resistant prostate cancer

2019 ◽  
Author(s):  
Mitchell G Lawrence ◽  
Laura H Porter ◽  
Daisuke Obinata ◽  
Shahneen Sandhu ◽  
Luke A Selth ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
New Combination ◽  
Combination Therapies ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant
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