Analysis of cabazitaxel‐resistant mechanism in human castration‐resistant prostate cancer

Hongo, Hiroshi; Kosaka, Takeo; Oya, Mototsugu

doi:10.1111/cas.13729

Cited by 30 publications

(40 citation statements)

References 21 publications

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“…Therefore, lipid signaling and metabolic pathways may serve as new targets for the development of therapeutics to treat PCa. Current treatment modalities for PCa consist of anti‐androgen and chemotherapeutic interventions, yet metastatic prostate tumors often develop resistance to taxane chemotherapeutics . Combination therapies consisting of taxanes and novel agents could present an opportunity to enhance antitumor efficacy while simultaneously lowering taxane doses and potentially reducing taxane‐resistance in metastatic PCa …”

Section: Discussionmentioning

confidence: 99%

“…Docetaxel and cabazitaxel are used as standard chemotherapeutics for the treatment of naïve castration‐resistant PCa . Despite the clinical availability of docetaxel, cabazitaxel, and newer‐generation taxane chemotherapeutics, prostate tumors often develop resistance to these agents . Therefore, combination therapies consisting of docetaxel/cabazitaxel and other chemotherapeutic agents could lead to enhanced antitumor efficacy or permit the use of lower taxane doses in patients, thus reducing taxane‐resistance as well as potentially decreasing the adverse effects associated with taxane chemotherapeutics .…”

Section: Introductionmentioning

confidence: 99%

“…[19][20][21][22][23] Despite the clinical availability of docetaxel, cabazitaxel, and newer-generation taxane chemotherapeutics, prostate tumors often develop resistance to these agents. 20,24 Therefore, F I G U R E 1 SBFI-102/SBFI-103 structures and in vitro affinities (K i , µM), and docetaxel/cabazitaxel structures. The chemical structures and K i values of (A) SBFI-102 and (B) SBFI-103 are shown and taken from Yan et al 17 The chemical structures for (C) docetaxel and (D) cabazitaxel.…”

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confidence: 99%

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Docetaxel/cabazitaxel and fatty acid binding protein 5 inhibitors produce synergistic inhibition of prostate cancer growth

et al. 2019

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Background Prostate cancer (PCa) remains the second leading cause of cancer‐related death among men. Taxanes, such as docetaxel and cabazitaxel are utilized in standard treatment regimens for chemotherapy naïve castration‐resistant PCa. However, tumors often develop resistance to taxane chemotherapeutics, highlighting a need to identify additional therapeutic targets. Fatty acid‐binding protein 5 (FABP5) is an intracellular lipid carrier whose expression is upregulated in metastatic PCa and increases cell growth, invasion, and tumor formation. Here, we assessed whether FABP5 inhibitors synergize with semi‐synthetic taxanes to induce cytotoxicity in vitro and attenuate tumor growth in vivo. Methods PC3, DU‐145, and 22Rv1 PCa cells were incubated with FABP5 inhibitors Stony Brook fatty acid‐binding protein inhibitor 102 (SBFI‐102) or SBFI‐103 in the presence or absence of docetaxel or cabazitaxel, and cytotoxicity was evaluated using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5 diphenyl tetrazolium bromide assay. Cytotoxicity of SBFI‐102 and SBFI‐103 was also evaluated in noncancerous cells. For the in vivo studies, PC3 cells were subcutaneously implanted into BALB/c nude mice, which were subsequently treated with FABP5 inhibitors, docetaxel, or a combination of both. Results SBFI‐102 and SBFI‐103 produced cytotoxicity in the PCa cells. Coincubation of the PCa cells with FABP5 inhibitors and docetaxel or cabazitaxel produced synergistic cytotoxic effects in vitro. Treatment of mice with FABP5 inhibitors reduced tumor growth and a combination of FABP5 inhibitors with a submaximal dose of docetaxel reduced tumor growth to a larger extent than treatment with each drug alone. Conclusions FABP5 inhibitors increase the cytotoxic and tumor‐suppressive effects of taxanes in PCa cells. The ability of these drugs to synergize could permit more efficacious antitumor activity while allowing for dosages of docetaxel or cabazitaxel to be lowered, potentially decreasing taxane‐resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Docetaxel/cabazitaxel and fatty acid binding protein 5 inhibitors produce synergistic inhibition of prostate cancer growth

et al. 2019

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“…The DU145CR and PC3CR cell lines were established by culturing the DU145 and PC-3 cells, respectively, with increasing concentrations of cabazitaxel (0.3–3 µM) for 2 years [106]. The DU145CR cells show resistance to cabazitaxel-induced G2/M cell cycle arrest through ERK signaling activation.…”

Section: Pca Cell Linesmentioning

confidence: 99%

Application of Prostate Cancer Models for Preclinical Study: Advantages and Limitations of Cell Lines, Patient-Derived Xenografts, and Three-Dimensional Culture of Patient-Derived Cells

Namekawa

Ikeda

Horie‐Inoue

et al. 2019

Cells

126

109

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Various preclinical models have been developed to clarify the pathophysiology of prostate cancer (PCa). Traditional PCa cell lines from clinical metastatic lesions, as exemplified by DU-145, PC-3, and LNCaP cells, are useful tools to define mechanisms underlying tumorigenesis and drug resistance. Cell line-based experiments, however, have limitations for preclinical studies because those cells are basically adapted to 2-dimensional monolayer culture conditions, in which the majority of primary PCa cells cannot survive. Recent tissue engineering enables generation of PCa patient-derived xenografts (PDXs) from both primary and metastatic lesions. Compared with fresh PCa tissue transplantation in athymic mice, co-injection of PCa tissues with extracellular matrix in highly immunodeficient mice has remarkably improved the success rate of PDX generation. PDX models have advantages to appropriately recapitulate the molecular diversity, cellular heterogeneity, and histology of original patient tumors. In contrast to PDX models, patient-derived organoid and spheroid PCa models in 3-dimensional culture are more feasible tools for in vitro studies for retaining the characteristics of patient tumors. In this article, we review PCa preclinical model cell lines and their sublines, PDXs, and patient-derived organoid and spheroid models. These PCa models will be applied to the development of new strategies for cancer precision medicine.

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“…1,2 Unlike docetaxel, CTX is not pumped out by P-glycoprotein (P-gp) after endocytosis by cells due to its low substrate affinity for P-gp. 3,4 CTX was approved by the US Food and Drug Administration (FDA) to treat prostate cancer in 2010. However, its clinical application has been limited due to low solubility.…”

Section: Introductionmentioning

confidence: 99%

Folic acid receptor-targeted human serum albumin nanoparticle formulation of cabazitaxel for tumor therapy

Sun¹,

Zhao²,

Teng³

et al. 2018

IJN

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BackgroundWe previously developed cabazitaxel (CTX)-loaded human serum albumin nanoparticles (NPs-CTX) via a self-assembly method, and these NPs showed efficacy in prostate cancer therapy. Many studies have shown that the levels of folic acid (FA) receptor on the surface of various tumor cells are high. Therefore, FA-modified NPs-CTX may have enhanced antitumor effects compared with unmodified NPs-CTX.MethodsNPs-CTX were first prepared via self-assembly, and FA was conjugated on the surface of NPs-CTX through the -NH2 groups of the NPs to produce FA-NPs-CTX. The FA-NPs-CTX were evaluated in tumor cells with high FA receptor (FR) expression in vitro and in vivo.ResultsBoth NPs-CTX and FA-NPs-CTX exhibited good stability and morphology. Drug release from the NPs was not affected by FA conjugation. Compared with CTX dissolved in a mixture of Tween 80 and 13% ethanol (w/w) at a ratio of 1:4 (v/v) (Tween-CTX), the two nanoformulations had lower lytic activity against normal red blood cells. However, FA-NPs-CTX showed greater inhibition of tumor cells with overexpressed FR, compared with NPs-CTX, in the cytotoxicity experiments. Moreover, the cellular uptake of FA-NPs-CTX was enhanced through FR-mediated endocytosis in HeLa cells in vitro and HeLa xenograft tumors in vivo. Although Tween-CTX exhibited tumor growth inhibition similar to FA-NPs-CTX in vivo, this inhibition also caused adverse side effects; the median lethal dose (LD50) of Tween-CTX to mice was 5.68 mg/kg, while FA-NPs-CTX-treated mice survived at doses exceeding 400 mg/kg.ConclusionThe results showed that FA-NPs-CTX caused inhibition of tumor growth in a manner similar to that of Tween-CTX; however, the safety and tolerability of CTX were greatly improved by FA conjugation compared with those of Tween-CTX. In summary, FA-NPs-CTX have great potential in CTX delivery, and this formulation is a promising candidate for the treatment of cancers with high FR levels.

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Analysis of cabazitaxel‐resistant mechanism in human castration‐resistant prostate cancer

Cited by 30 publications

References 21 publications

Docetaxel/cabazitaxel and fatty acid binding protein 5 inhibitors produce synergistic inhibition of prostate cancer growth

Docetaxel/cabazitaxel and fatty acid binding protein 5 inhibitors produce synergistic inhibition of prostate cancer growth

Application of Prostate Cancer Models for Preclinical Study: Advantages and Limitations of Cell Lines, Patient-Derived Xenografts, and Three-Dimensional Culture of Patient-Derived Cells

Folic acid receptor-targeted human serum albumin nanoparticle formulation of cabazitaxel for tumor therapy

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