Hierarchical Self-Assembly of BODIPY Dyes as a Tool to Improve the Antitumor Activity of Capsaicin in Prostate Cancer

2018 ◽  
Vol 57 (52) ◽  
pp. 17235-17239 ◽  
Author(s):  
Angel Sampedro ◽  
Ágata Ramos-Torres ◽  
Christian Schwöppe ◽  
Christian Mück-Lichtenfeld ◽  
Ingo Helmers ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Self Assembly

scholarly journals Context-Specific Efficacy of Apalutamide Therapy in Preclinical Models of Pten-Deficient Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3975
Author(s):  
Marco A. De Velasco ◽  
Yurie Kura ◽  
Naomi Ando ◽  
Noriko Sako ◽  
Eri Banno ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Late Stage ◽  
Early Stage ◽  
Castration Resistant Prostate Cancer ◽  
Akt Inhibitor ◽  
Molecular Features ◽  
Context Specific

Significant improvements with apalutamide, a nonsteroidal antiandrogen used to treat patients suffering from advanced prostate cancer (PCa), have prompted evaluation for additional indications and therapeutic development with other agents; however, persistent androgen receptor (AR) signaling remains problematic. We used autochthonous mouse models of Pten-deficient PCa to examine the context-specific antitumor activity of apalutamide and profile its molecular responses. Overall, apalutamide showed potent antitumor activity in both early-stage and late-stage models of castration-naïve prostate cancer (CNPC). Molecular profiling by Western blot and immunohistochemistry associated persistent surviving cancer cells with upregulated AKT signaling. While apalutamide was ineffective in an early-stage model of castration-resistant prostate cancer (CRPC), it tended to prolong survival in late-stage CRPC. Molecular features associated with surviving cancer cells in CRPC included upregulated aberrant-AR, and phosphorylated S6 and proline-rich Akt substrate of 40 kDa (PRAS40). Strong synergy was observed with the pan-AKT inhibitor GSK690693 and apalutamide in vitro against the CNPC- and CRPC-derived cell lines and tended to improve the antitumor responses in CNPC but not CRPC in vivo. Upregulation of signal transducer and activator of transcription 3 (STAT3) and proviral insertion in murine-1 (PIM-1) were associated with combined apalutamide/GSK690693. Our findings show that apalutamide can attenuate Pten-deficient PCa in a context-specific manner and provides data that can be used to further study and, possibly, develop additional combinations with apalutamide.

318 Olaparib plus pembrolizumab in patients with previously treated advanced solid tumors with homologous recombination repair mutation and/or homologous recombination repair deficiency: KEYLYNK-007

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A344-A344
Author(s):  
Timothy A Yap ◽  
Mallika Dhawan ◽  
Andrew E Hendifar ◽  
Michele Maio ◽  
Taofeek K Owonikoko ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Homologous Recombination ◽  
Antitumor Activity ◽  
Solid Tumors ◽  
Homologous Recombination Repair ◽  
Advanced Solid Tumors ◽  
Repair Deficiency ◽  
Recombination Repair ◽  
Modified Recist ◽  
Previously Treated

BackgroundTreatment with the anti–PD-1 antibody pembrolizumab has improved clinical outcomes in multiple previously treated advanced solid tumors. The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib has shown antitumor activity as monotherapy in patients with previously treated advanced ovarian, breast, pancreatic, and prostate cancers with BRCA1/BRCA2 mutations (BRCAm). Activity was also seen in patients with previously treated advanced solid tumors with other homologous recombination repair mutation (HRRm) and in those with ovarian cancer with homologous recombination repair deficiency (HRD) phenotype. PARP inhibitors have been found to increase interferon signaling and tumor infiltrating lymphocytes, enhancing tumor susceptibility to immune checkpoint blockade. Antitumor activity of PD-(L)1 plus PARP inhibition was found to be higher than expected with either agent alone in patients with recurrent ovarian cancer regardless of BRCAm or HRD status and in patients with BRCAm breast cancer. KEYLYNK-007 (NCT04123366) evaluates the antitumor activity and safety of olaparib in combination with pembrolizumab in patients with previously treated advanced solid tumors with HRRm and/or HRD.MethodsThis phase 2, nonrandomized, multicenter, open-label study will enroll approximately 300 patients aged ≥18 years with histologically/cytologically confirmed, previously treated, advanced solid tumors with HRRm and/or HRD per Lynparza HRR-HRD assay (Foundation Medicine, Inc., Cambridge, MA, USA), with an ECOG PS of 0-1. Patients will be grouped by biomarker status: subgroup 1: BRCAm; subgroup 2: HRRm without BRCAm; and subgroup 3: HRD positive without HRRm (loss of heterozygosity score ≥16 per Lynparza HRR-HRD assay). Patients will receive olaparib 300 mg twice daily + pembrolizumab 200 mg intravenously Q3W (35 cycles) until PD, unacceptable AEs, intercurrent illness, investigator decision, withdrawal of consent, or pregnancy. Tumor imaging assessment by blinded independent central review (BICR) per RECIST v1.1 or Prostate Cancer Working Group (PCWG)–modified RECIST v1.1 for prostate cancer will occur Q9W for 12 months, then Q12W until PD, start of new anticancer treatment, withdrawal of consent, pregnancy, or death. AEs will be monitored throughout the study and for 30 days after final dose (90 days for serious AEs). The primary endpoint is ORR (RECIST v1.1 or PCWG–modified RECIST version 1.1 by BICR). Secondary endpoints include duration of response (DOR) and PFS (RECIST v1.1 or PCWG–modified RECIST v1.1 by BICR), OS, and safety. Point estimate and exact Clopper-Pearson CI for ORR, and Kaplan-Meier estimates for DOR, PFS, and OS will be calculated. A total of 89 sites are currently enrolling in 20 countries.ResultsN/AConclusionsN/ATrial RegistrationClinicalTrials. gov identifier, NCT04123366Ethics ApprovalAn independent institutional review board or ethics committee approved the protocol at each study site, and the trial is being conducted in compliance with Good Clinical Practice guidelines and the Declaration of Helsinki.

scholarly journals Quercetin, a Flavonol, Promotes Disassembly of Microtubules in Prostate Cancer Cells: Possible Mechanism of its Antitumor Activity.

1998 ◽  
Vol 31 (5) ◽  
pp. 435-445 ◽  
Author(s):  
Tetsuo Takagi ◽  
Susumu Takekoshi ◽  
Takeshi Okabe ◽  
Hidetaka Nagata ◽  
Takao Honma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Prostate Cancer Cells

scholarly journals Antitumor Activity and Mechanism of Action of Hormonotoxin, an LHRH Analog Conjugated to Dermaseptin-B2, a Multifunctional Antimicrobial Peptide

2021 ◽  
Vol 22 (21) ◽  
pp. 11303
Author(s):  
Mickael Couty ◽  
Marie Dusaud ◽  
Mickael Miro-Padovani ◽  
Liuhui Zhang ◽  
Patricia Zadigue ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Antimicrobial Peptide ◽  
Tumor Cell Line ◽  
Ic50 Value ◽  
Experimental Approaches ◽  
Innovative Drugs ◽  
Therapeutic Alternatives ◽  
Apoptotic Mechanism

Prostate cancer is the most common cancer in men. For patients with advanced or metastatic prostate cancer, available treatments can slow down its progression but cannot cure it. The development of innovative drugs resulting from the exploration of biodiversity could open new therapeutic alternatives. Dermaseptin-B2, a natural multifunctional antimicrobial peptide isolated from Amazonian frog skin, has been reported to possess antitumor activity. To improve its pharmacological properties and to decrease its peripheral toxicity and lethality we developed a hormonotoxin molecule composed of dermaseptin-B2 combined with d-Lys6-LHRH to target the LHRH receptor. This hormonotoxin has a significant antiproliferative effect on the PC3 tumor cell line, with an IC50 value close to that of dermaseptin-B2. Its antitumor activity has been confirmed in vivo in a xenograft mouse model with PC3 tumors and appears to be better tolerated than dermaseptin-B2. Biophysical experiments showed that the addition of LHRH to dermaseptin-B2 did not alter its secondary structure or biological activity. The combination of different experimental approaches indicated that this hormonotoxin induces cell death by an apoptotic mechanism instead of necrosis, as observed for dermaseptin-B2. These results could explain the lower toxicity observed for this hormonotoxin compared to dermaseptin-B2 and may represent a promising targeting approach for cancer therapy.

Induction of protective antitumor activity of tumor lysate-pulsed dendritic cells vaccine in RM-1 prostate cancer mode

2009 ◽  
Vol 24 (1) ◽  
pp. 18-24 ◽  
Author(s):  
Danfeng Xu ◽  
Yushan Liu ◽  
Yi Gao ◽  
Xingang Cui ◽  
Jizhang Xing ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dendritic Cells ◽  
Antitumor Activity ◽  
Tumor Lysate

Abstract 5130: Assessment of the antitumor activity of leech (huridinaria manillensis) saliva extract in prostate cancer

2015 ◽  
Author(s):  
Amr E. Ammar ◽  
Mohamed H. Hassona ◽  
Gray R. Meckling ◽  
Leslie G. Chan ◽  
Mei Y. Chin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity

Abstract B19: Induction of apoptosis and antitumor activity of the AKT inhibitor AZD5363 is enhanced by combination with hormonal therapies in preclinical models of prostate cancer

2012 ◽  
Vol 72 (4 Supplement) ◽  
pp. B19-B19
Author(s):  
Claire Crafter ◽  
Barry R. Davies ◽  
Christian Thomas ◽  
Francois Lamoureux ◽  
Hannah Greenwood ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Preclinical Models ◽  
Akt Inhibitor ◽  
Induction Of Apoptosis ◽  
Hormonal Therapies
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