Serum exosomal P-glycoprotein is a potential marker to diagnose docetaxel resistance and select a taxoid for patients with prostate cancer

Kato, Taku; Mizutani, Kosuke; Kameyama, Koji; Kawakami, Kyojiro; Fujita, Yasunori; Nakane, Keita; Kanimoto, Yusuke; Ehara, Hidetoshi; Ito, Hiroyasu; Seishima, Mitsuru; Deguchi, Takashi; Ito, Masafumi

doi:10.1016/j.urolonc.2015.04.019

Cited by 94 publications

(91 citation statements)

References 34 publications

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“…Fully understanding to what degree ABCB1 expression levels mediate resistance to each drug may allow for stratification of patients between the two or lead to decisions to try alternative therapies, thus preventing decisions to treat when success is unlikely. Proof of principle studies detecting higher ABCB1 levels in blood or serum samples from docetaxel resistant prostate cancer patients have been performed thus making it feasible considering our novel findings to continue studying ABCB1 expression as a prognostic marker of taxane sensitivity (25, 26). …”

Section: Discussionmentioning

confidence: 99%

ABCB1 Mediates Cabazitaxel–Docetaxel Cross-Resistance in Advanced Prostate Cancer

Lombard

Liu

Armstrong

et al. 2017

Molecular Cancer Therapeutics

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Advancements in research have added several new therapies for castration-resistant prostate cancer (CRPC), greatly augmenting our ability to treat patients. However, CRPC remains an incurable disease due to the development of therapeutic resistance and the existence of cross-resistance between available therapies. Understanding the interplay between different treatments will lead to improved sequencing and the creation of combinations which overcome resistance and prolong survival. Whether there exists cross-resistance between docetaxel and the next-generation taxane cabazitaxel is poorly understood. In this study, we use C4-2B and DU145 derived docetaxel-resistant cell lines to test response to cabazitaxel. Our results demonstrate that docetaxel resistance confers cross-resistance to cabazitaxel. We show that increased ABCB1 expression is responsible for cross-resistance to cabazitaxel and that inhibition of ABCB1 function through the small molecule inhibitor elacridar re-sensitizes taxane resistant cells to treatment. Additionally, the anti-androgens bicalutamide and enzalutamide, previously demonstrated to be able to re-sensitize taxane resistant cells to docetaxel through inhibition of ABCB1 ATPase activity, are also able to re-sensitize resistant cells to cabazitaxel treatment. Lastly, we show that re-sensitization using an anti-androgen is far more effective in combination with cabazitaxel than docetaxel. Collectively, these results address key concerns in the field including that of cross-resistance between taxanes and highlighting a mechanism of cabazitaxel resistance involving ABCB1. Furthermore, these preclinical studies suggest the potential in utilizing combinations of anti-androgens with cabazitaxel for increased effect in treating advanced CRPC.

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Section: Discussionmentioning

confidence: 99%

ABCB1 Mediates Cabazitaxel–Docetaxel Cross-Resistance in Advanced Prostate Cancer

Lombard

Liu

Armstrong

et al. 2017

Molecular Cancer Therapeutics

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“…Exosomal serum MDR-1 , MDR-3 and PABP4 proteins were enriched in docetaxel-resistant CRPC patients relative to doxetaxel-sensitive patients [123]. Another study found that serum exosomal P-glycoprotein were higher in docetaxel-resistant patients than therapy-naïve patients [124], indicating that exosomal P-glycoprotein may be a potential marker for docetaxel resistance.…”

Section: Exosomesmentioning

confidence: 99%

Liquid biopsy: a step forward towards precision medicine in urologic malignancies

et al. 2017

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There is a growing trend towards exploring the use of a minimally invasive “liquid biopsy” to identify biomarkers in a number of cancers, including urologic malignancies. Multiple aspects can be assessed in circulating cell-free DNA, including cell-free DNA levels, integrity, methylation and mutations. Other prospective liquid biopsy markers include circulating tumor cells, circulating RNAs (miRNA, lncRNAs and mRNAs), cell-free proteins, peptides and exosomes have also emerged as non-invasive cancer biomarkers. These circulating molecules can be detected in various biological fluids, including blood, urine, saliva and seminal plasma. Liquid biopsies hold great promise for personalized medicine due to their ability to provide multiple non-invasive global snapshots of the primary and metastatic tumors. Molecular profiling of circulating molecules has been a stepping-stone to the successful introduction of several non-invasive multi-marker tests into the clinic. In this review, we provide an overview of the current state of cell-free DNA-based kidney, prostate and bladder cancer biomarker research and discuss the potential utility other circulating molecules. We will also discuss the challenges and limitations facing non-invasive cancer biomarker discovery and the benefits of this growing area of translational research.

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“…ABCB1, ABCB4, PABPC4 and SH3GL1 are much more sufficient in EVs from docetaxel-resistant prostate cancer cell lines and potentially higher in serum EVs in men with docetaxel-resistant PCa. 148 AR-V7 is correlated with resistance to enzalutamide and abiraterone in metastatic CRPC patients, which could be a biomarker to predict the CRPC. 176,177 Finally, EVs-derived PCs can be used as vaccine vesicles that present prostate-associated antigens such as PSA and PAP on their membrane to exert an anti-tumour immune response.…”

Section: Pros Tate C An Cermentioning

confidence: 96%

“…tensin homolog gene (PTEN), survivin and other factors with decreased level compared to benign prostatic hyperplasia or health subjects 133,[147][148][149]. PC-based EVs show great value in comprehensively mapping nucleic acid changes in PCa via urine-or blood-based liquid biopsies, and it has been known that the EVs is important pool resource for circulating-free DNA (cfDNA)150 ; as such, some fac-Several mRNAs could be recognized as promising diagnostic and prognostic tools for the PCa[152][153][154][155][156] ; for instance, the transcripts of CDH3 from EVs were significantly decreased compared with benign hyperplasia 156 ; contrarily, the mRNA level of PTEN gene can only be detected in the patient of PC,147 and nevertheless, both of them are expected to be powerful for the diagnosis and monitoring of PCa.…”

mentioning

confidence: 99%

Extracellular vesicles in urologic malignancies—Implementations for future cancer care

Zhang

Xia

et al. 2019

Cell Proliferation

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Extracellular vesicles (EVs), a heterogeneous group of vesicles differing in size and shape, cargo content and function, are membrane‐bound and nano‐sized vesicles that could be released by nearly all variations of cells. EVs have gained considerable attention in the past decades for their functions in modulating intercellular signalling and roles as potential pools for the novel diagnostic and prognostic biomarkers, as well as therapeutic targets in several cancers including urological neoplasms. In general, human and animal cells both can release distinct types of EVs, including exosomes, microvesicles, oncosomes and large oncosomes, and apoptotic bodies, while the content of EVs can be divided into proteins, lipids and nucleic acids. However, the lack of standard methods for isolation and detection platforms rein the widespread usage in clinical applications warranted furthermore investigations in the development of reliable, specific and sensitive isolation techniques. Whether and how the EVs work has become pertinent issues. With the aid of high‐throughput proteomics or genomics methods, a fully understanding of contents contained in EVs from urogenital tumours, beyond all doubt, will improve our ability to identify the complex genomic alterations in the process of cancer and, in turn, contribute to detect potential therapeutic target and then provide personalization strategy for patient.

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Serum exosomal P-glycoprotein is a potential marker to diagnose docetaxel resistance and select a taxoid for patients with prostate cancer

Cited by 94 publications

References 34 publications

ABCB1 Mediates Cabazitaxel–Docetaxel Cross-Resistance in Advanced Prostate Cancer

ABCB1 Mediates Cabazitaxel–Docetaxel Cross-Resistance in Advanced Prostate Cancer

Liquid biopsy: a step forward towards precision medicine in urologic malignancies

Extracellular vesicles in urologic malignancies—Implementations for future cancer care

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