Efficacy of Cabazitaxel in Castration-resistant Prostate Cancer Is Independent of the Presence of AR-V7 in Circulating Tumor Cells

Onstenk, Wendy; Sieuwerts, Anieta M.; Kraan, Jaco; Van, Mai; Nieuweboer, Annemieke J.M.; Mathijssen, Ron H.J.; Hamberg, Paul; Meulenbeld, Hielke J.; Laere, Bram De; Dirix, Luc; Soest, Robert J. van; Lolkema, Martijn P.; Martens, John W.M.; Weerden, Wytske M. van; Jenster, Guido; Foekens, John A.; Wit, Ronald de; Sleijfer, Stefan

doi:10.1016/j.eururo.2015.07.007

Cited by 222 publications

(192 citation statements)

References 26 publications

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“…70 The data from recent studies suggested that patients harboring AR-V7 in CTCs have a higher likelihood of primary resistance to ASIs and might be considered for taxane therapy, implying clinical use as a reliable biomarker for precision medicine. [71][72][73] The AR-V7 assays, however, require further refinement before they are ready for clinical use. Furthermore, ctDNA analyses assessing AR amplification and/or mutation in univariate analyses also appear to be prognostic for a poorer response to ASIs.…”

Section: Cross-resistance Between Classes Of Agentsmentioning

confidence: 99%

Current treatment strategies for advanced prostate cancer

et al. 2017

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During the past decade, treatment strategies for patients with advanced prostate cancer involving stage IV (T4N0M0, N1M0 or M1) hormone-sensitive prostate cancer and recurrent prostate cancer after treatment with curative intent, as well as castration-resistant prostate cancer, have extensively evolved with the introduction and approval of several new agents including sipuleucel-T, radium-223, abiraterone, enzalutamide and cabazitaxel, all of which have shown significant improvement on overall survival. The appropriate use of these agents and the proper sequencing of these agents are still not optimized. The results of several recently reported randomized controlled trials and retrospective studies could assist in developing a treatment strategy for advanced prostate cancer. In addition, prospective studies and molecular characterization of tumors to address these issues are ongoing.

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Section: Cross-resistance Between Classes Of Agentsmentioning

confidence: 99%

Current treatment strategies for advanced prostate cancer

et al. 2017

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“…AR-V7 lacking the AR LBD still retains the ability to activate transcriptions of its target genes. Antonarakis et al found that AR-V7 conferred resistance to abiraterone and enzalutamide in metastatic CRPC, not to taxane [4] and cabazitaxel [9]. Constant expression of AR-v567es in the benign prostate tissues may induce epithelial hyperplasia and invasive adenocarcinoma [10].…”

Section: Ar Amplification Mutants and Variantsmentioning

confidence: 99%

Darwinian Selection in Prostate Cancer and Medical Treatment

Song¹

2017

IJCM

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Organisms evolved into different species to adapt to the environment according to the laws of Darwinian evolution. In a single life, prostate cancer cells can also evolve into tumor stem cells to adapt to the microenvironment, such as different chemotherapeutic drugs. These cancer cells become an unrestricted growth group relatively independent of the individual. The present review attempts to establish evidence that prostate cancer cells may survive by hormonotherapy and chemotherapy by gene amplification, mutation, and alternative splicing. Simultaneously, novel treatment strategies have been cited and evaluated, avoiding the resistance mechanisms.

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“…Mutations or amplification of the AR can cause resistance to androgen-deprivation therapy and are detectable in CTCs [145]. Moreover, recent studies have shown that mRNA expression of AR-V7, a truncated mRNA splice variant of AR that lacks the ligand-binding domain but remains constitutively active, in CTCs may predict failure of treatment with enzalutamide and abiraterone [146,147], but retained sensitivity to cytotoxic taxanes such as docetaxel [81,[148][149][150]. In addition, a point mutation (F876L) in the ligand-binding domain of AR confers resistance to enzalutamide [151,152].…”

Section: Therapeutic Targets and Resistance Mechanismsmentioning

confidence: 99%

The promise of circulating tumor cells for precision cancer therapy

Hwang

Miyamoto

2016

Biomarkers in Medicine

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The rapidly growing array of therapeutic options in cancer requires informative biomarkers to guide the rational selection and precision application of appropriate therapies. Circulating biomarkers such as circulating tumor cells have immense potential as noninvasive, serial 'liquid biopsies' that may be more representative of the complete spectrum of a patient's individual malignancy than spatially and temporally restricted tumor biopsies. In this review, we discuss the current state-of-the-art in the isolation and molecular characterization of circulating tumor cells as well as their utility in a wide range of clinical applications such as prognostics, treatment monitoring and identification of novel therapeutic targets and resistance mechanisms to enable real-time adjustments in the clinical management of cancer. The evolving landscape of cancer therapy creates an urgent need for minimally invasive biomarkers to facilitate early detection, prognosis and prediction of therapeutic response and resistance to enable highly adaptable, real-time precision therapy [1]. The conventional gold standard of using single biopsies of the primary tumor to inform all downstream therapeutic decisions may no longer be adequate given increasing evidence of significant spatial and temporal hetero geneity in tumors [2], especially when placed under the selection pressure of various treatments. Moreover, serial biopsies are often impractical, morbid and technically challenging.In this review, we focus on the emerging role of circulating tumor cells (CTCs), which can be serially obtained from minimally invasive blood draws or 'liquid biopsies'. CTCs are cancer cells that have been shed into the peripheral circulation from primary or metastatic tumors [3,4]. The first reported observation of CTCs was in 1869 by Australian pathologist Thomas Ashworth at the autopsy of a patient with metastatic cancer [5]. By comparing the morphology of circulating cells with those from different cancerous lesions, Ashworth came to the prescient conclusion that 'cells identical with those of the cancer itself being seen in the blood may tend to throw some light upon the mode of origin of multiple tumors existing in the same person' [5]. Indeed, molecular analyses of CTCs may be superior to individual tumor biopsies because these circulating cells likely provide a sampling of different regions of the primary tumor as well as metastatic deposits, and therefore are more likely to capture the genetic heterogeneity of a patient's cancer.While cell-free circulating tumor DNA (ctDNA) is an important, complementary biomarker to CTCs, it has been reviewed extensively elsewhere and will not be discussed in this review [4,6]. Moreover, although ctDNA may in some cases be more reliably [7], they are largely limited to genomic mutational analysis. In contrast, CTC analysis can provide a wealth of other information including cell morphology, immunocytochemical phenotype, presence of important epitopes, presence of multiple mutations within a single cell to decode ...

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Efficacy of Cabazitaxel in Castration-resistant Prostate Cancer Is Independent of the Presence of AR-V7 in Circulating Tumor Cells

Cited by 222 publications

References 26 publications

Current treatment strategies for advanced prostate cancer

Current treatment strategies for advanced prostate cancer

Darwinian Selection in Prostate Cancer and Medical Treatment

The promise of circulating tumor cells for precision cancer therapy

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