Detecting predictive androgen receptor modifications in circulating prostate cancer cells

Steinestel, Julie; Luedeke, Manuel; Arndt, Annette; Schnoeller, Thomas; Lennerz, Jochen K.; Wurm, Carina; Maier, Christiane; Cronauer, Marcus V.; Steinestel, Konrad; Schrader, Andres Jan

doi:10.18632/oncotarget.3925

Cited by 123 publications

(97 citation statements)

References 29 publications

(25 reference statements)

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“…Some studies remark the role of molecular modifications that cause resistance to androgen deprivation therapy, mainly in the AR [26]. Other studies demonstrate the effectiveness of PCA3, PSGR (OR51E2), and PSMA (FOLH1) expression levels in urine sediment as biomarkers for the detection of PCa in benign prostatic hyperplasia [20].…”

Section: Discussionmentioning

confidence: 99%

Association between RNASEL, MSR1, and ELAC2 single nucleotide polymorphisms and gene expression in prostate cancer risk

Álvarez-Cubero

Pascual-Geler

Martínez-González

et al. 2016

Urologic Oncology: Seminars and Original Investigations

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Section: Discussionmentioning

confidence: 99%

Association between RNASEL, MSR1, and ELAC2 single nucleotide polymorphisms and gene expression in prostate cancer risk

Álvarez-Cubero

Pascual-Geler

Martínez-González

et al. 2016

Urologic Oncology: Seminars and Original Investigations

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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

Biomark. Med.

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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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“…Also, median PFS, clinical or radiographic PFS, and median OS were significantly lower in the AR-V7-positive group as compared to the AR-V7-negative group. However, these data need external validation in a larger cohort of patients since a recently published study reported a 10% response rate to AA/P or ENZ in AR-V7-positive patients [73]. …”

Section: Mechanisms Of Resistance and Sequencing Treatment Strategiesmentioning

confidence: 99%

Systemic Medical Treatment in Men with Metastatic Castration-Resistant Prostate Cancer: Recommendations for Daily Routine

Herden

Heidegger²,

Paffenholz³

et al. 2015

Oncol Res Treat

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The approval or clinical evaluation of several new agents - cabazitaxel, abiraterone acetate, enzalutamide, sipuleucel-T, and radium-223 - has significantly changed the management of patients with metastatic castration-resistant prostate cancer (mCRPC) prior to or after docetaxel-based chemotherapy. All of these agents have resulted in a significant survival benefit as compared to their control group. However, treatment responses might differ depending on the associated comorbidities and the extent and biological aggressiveness of the disease. Furthermore, treatment-associated side effects differ between the various drugs. As new drugs become approved, new treatment strategies and markers to best select which patients will best respond to which drug are needed. It is the aim of the current article to i) summarize the data of established treatment options in mCRPC, ii) highlight new developments in medical treatment, iii) provide clinically useful algorithms for the daily routine, and iv) point out future developments in medical treatment.

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Detecting predictive androgen receptor modifications in circulating prostate cancer cells

Cited by 123 publications

References 29 publications

Association between RNASEL, MSR1, and ELAC2 single nucleotide polymorphisms and gene expression in prostate cancer risk

Association between RNASEL, MSR1, and ELAC2 single nucleotide polymorphisms and gene expression in prostate cancer risk

The Promise of Circulating Tumor Cells for Precision Cancer Therapy

Systemic Medical Treatment in Men with Metastatic Castration-Resistant Prostate Cancer: Recommendations for Daily Routine

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