Dataset Information

Analysis of cabazitaxel-resistant mechanism in human castration-resistant prostate cancer.

ABSTRACT: Cabazitaxel (CBZ) is approved for docetaxel-resistant castration-resistant prostate cancer (CRPC). However, efficacy of CBZ for CRPC is limited and there are no effective treatments for CBZ-resistant CRPC. In order to investigate the CBZ-resistant mechanism, the establishment of a CBZ-resistant cell line is urgently needed. We established CBZ-resistant CRPC cell lines DU145CR and PC3CR by incubating DU145 and PC3 cells with gradually increasing concentrations of CBZ for approximately 2 years. We analyzed the gene expression profiles and cell cycle changes using microarray and flow cytometry. Pathway analysis revealed DU145CR cells had enhanced gene clusters of cell division and mitotic nuclear division. Enhancement of ERK signaling was detected in DU145CR cells. DU145CR cells had resistance to G₂ /M arrest induced by CBZ through ERK signaling activation. The MEK inhibitor PD184352 significantly inhibited cell proliferation of DU145CR. In contrast to DU145CR, PC3CR cells had enhancement of PI3K/AKT signaling. The PI3K/mTOR inhibitor NVP-BEZ 235 had a significant antitumor effect in PC3CR cells. Cabazitaxel -resistant CRPC cells established in our laboratory had enhancement of cell cycle progression signals and resistance to G₂ /M arrest induced by CBZ. Enhancement of ERK signaling or PI3K/AKT signaling were detected in the cell lines, so ERK or PI3K/AKT could be therapeutic targets for CBZ-resistant CRPC.

SUBMITTER: Hongo H

PROVIDER: S-EPMC6125448 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Analysis of cabazitaxel-resistant mechanism in human castration-resistant prostate cancer.

Hongo Hiroshi H Kosaka Takeo T Oya Mototsugu M

Cancer science 20180806 9

Cabazitaxel (CBZ) is approved for docetaxel-resistant castration-resistant prostate cancer (CRPC). However, efficacy of CBZ for CRPC is limited and there are no effective treatments for CBZ-resistant CRPC. In order to investigate the CBZ-resistant mechanism, the establishment of a CBZ-resistant cell line is urgently needed. We established CBZ-resistant CRPC cell lines DU145CR and PC3CR by incubating DU145 and PC3 cells with gradually increasing concentrations of CBZ for approximately 2 years. We ...[more]

PMID: 29989268

Similar Datasets

Project description:Background:Several studies have reported the efficacy of cabazitaxel in cancer therapy; however, investigations of its safety are few. The aim of this study was to retrospectively analyze the efficacy and safety of cabazitaxel based on treatment outcome data. Methods:A questionnaire form on the use of cabazitaxel was mailed to hospitals associated with the Shinshu University. Responses were received from 11 institutions regarding 55 cases. Results:Patients received a median of 4 courses of cabazitaxel treatment. Decreases in prostrate-specific antigen (PSA) were observed in 61.5% of cases with declines of 30%, 50%, and 90% in 36.5%, 23.0%, and 7.6% of cases, respectively. PSA progression-free survival was 5.0 months, and overall survival after the start of cabazitaxel was 13.0 months. Forty-five patients received postcabazitaxel treatment; 17 showed decreased PSA. Safety assessment indicated that white blood cell and neutrophil counts were significantly higher in the second than in the first course of treatment and Grade 3 to 4 leukopenia and neutropenia significantly decreased. Twenty-four subjects were aged ?75 years; 79% of them had their doses reduced at the first administration. The mean dose was 20 mg/m2. However, there was no significant difference in the PSA progression-free survival between the ?75-year-old and <75-year-old groups. Patients in the ?75-year-old group, particularly those whose doses were not reduced, experienced several Grade 3 to 4 adverse effects. Ten patients discontinued treatment owing to adverse effects and systemic worsening. Conclusions:To use cabazitaxel effectively, starting administration as early as possible before disease progression is important, and even if Grade 3 to 4 leukopenia and neutropenia are observed during the first course, it is important to carefully maintain the dose. Even when treating elderly patients, reducing the dose does not reduce therapeutic efficacy. However, because this cohort experienced several ? Grade 3 adverse effects, a great deal of caution is required.

Dataset Information

Analysis of cabazitaxel-resistant mechanism in human castration-resistant prostate cancer.

Publications

Analysis of cabazitaxel-resistant mechanism in human castration-resistant prostate cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets