Expression of somatostatin receptor subtypes, aurora kinase A, and interleukin-6 in prostate cancer before androgen ablation.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e564-e564
Author(s):  
Angela Gernone ◽  
Senia Trabucco ◽  
Leonardo Resta ◽  
Anna Napoli
Keyword(s):  
Prostate Cancer ◽  
Interleukin 6 ◽  
Single Cells ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Aurora Kinase ◽  
Receptor Subtypes ◽  
Aurora Kinase A ◽  
Androgen Ablation ◽  
Kinase A

e564 Background: Neuroendocrine differentiation (NED) in prostate cancer (PC) can be detected by immunohistochemistry as single cells in conventional adenocarcinoma. The extent of NED is associated with poor prognosis and early onset of castrate resistant prostate cancer. Aurora kinase A (AURKA) and Interleukin-6 (IL-6) cooperate to induce NED. The aim of this study was to correlate the expression of somatostatin receptor (SSTR) 1- 2- 3- 4- 5 subtypes, AURKA and IL-6 in primary PC with NED pattern and OS. Methods: PC tissues were reviewed from 60 pts who had undergone biopsy or radical prostatectomy for previously untreated advanced or metastatic PC from 2010 to 2016. 10 samples expressed histologically chromogranin A (CgA), a marker of NED expression. Median age was 67 years (47-80), Gleason score ≥ 7, median PSA was 60 ng/ml (1.3-1000), ECOG 0/1 and bone-visceral sites measurable in 90% of cases. For comparison purposes, 8 pathology specimens from pts with primary PC were used. Results: SSTR1-2-4-5 were detected in the nucleus of PC cells in 10/10 samples. SSTR3 and AURKA were not expressed in all 10 samples. IL-6 was detected in 9/10 samples. All 10 pts were associated with a more aggressive clinical course and OS was < 12 mos. Conclusions: In metastatic prostate cancer, pretreatment NED pattern can be a predictor for progression and survival after hormonal and chemotherapy. SSTRs and somatostatin analogs are not potential targets for prostate cancer.

Expression of androgen receptor, somatostatin receptor subtypes, aurora kinase A, and interleukin-6 in prostate cancer before androgen ablation.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16508-e16508
Author(s):  
Angela Gernone ◽  
Senia Trabucco ◽  
Eliano Cascardi ◽  
Leonardo Resta ◽  
Franco Silvestris ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Interleukin 6 ◽  
Somatostatin Receptor ◽  
Aurora Kinase ◽  
Androgen Deprivation ◽  
Aurora Kinase A ◽  
Androgen Ablation ◽  
Visceral Metastases ◽  
Kinase A

e16508 Background: Neuroendocrine differentiation (NED) in prostate cancer (PC) can be detected by immunohistochemistry as single cells in conventional adenocarcinoma. NEPC is a poor-recognized late presentation of hormone refractory subtype of PC AR-negative. NEPC correlates with poor prognosis, tumor progression during androgen-deprivation therapy and frequent visceral metastases. Aurora kinase A (AURKA) and Interleukin-6 (IL-6) cooperate to induce NED. The aim of this study was to correlate the expression of somatostatin receptor (SSTR) 1- 2- 3- 4- 5 subtypes, AURKA and IL-6 in primary PC with NED pattern before androgen ablation and OS. Methods: PC tissues were reviewed from 60 pts who had undergone biopsy or radical prostatectomy for previously untreated advanced or metastatic PC from 2010 to 2016. 10 samples expressed histologically chromogranin A (CgA), a marker of NED expression. Median age was 67 years (47-80), Gleason score ≥ 7, median PSA was 60 ng/ml (1.3-1000), ECOG 0/1 and bone-visceral sites measurable in 90% of cases. For comparison purposes, 8 pathology specimens from pts with primary PC negative for CgA expression were used. Results: SSTR1-2-4-5 were detected only in the nucleus of PC cells in 10/10 samples. AR was expressed in all 10 samples CgA positive. SSTR3 and AURKA were not expressed in all 10 samples. IL-6 was detected in 9/10 samples. All 10 pts developed early onset of CRPC, more aggressive clinical course with rapid occurrence of visceral metastases and OS was < 12 mos. Conclusions: In metastatic prostate cancer, pretreatment NED pattern can be a predictor for progression and survival after hormonal and during standard chemotherapy. Most likely NEPC become AR negative during disease progression and in response to androgen deprivation therapy. We supposed, according to other data, that the novel potent AR-targeted drugs should be not used in this subset of patients. SSTRs and somatostatin analogs are not potential targets for prostate cancer.

Prognostic role of somatostatin receptor subtypes in human prostate cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16120-e16120
Author(s):  
A. Gernone ◽  
V. Pagliarulo ◽  
S. Trabucco
Keyword(s):  
Prostate Cancer ◽  
Single Cells ◽  
Performance Status ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Neuroendocrine Differentiation ◽  
Patient Characteristics ◽  
Receptor Subtypes ◽  
Ecog Performance Status ◽  
Somatostatin Receptor Subtypes

e16120 Background: Neuroendocrine differentiation (NED) in prostate carcinoma (PC) is frequently detected by immunohistochemistry as single cells in conventional adenocarcinoma. NED of PC correlates with poor prognosis and tumor progression during androgen-deprivation therapy. The aim of our study was to correlate the expression of somatostatin receptor (SSTR) 1, 2, 3, 4, 5 subtypes in primary PC with NED pattern and Overall Survival (OS). Methods. PC tissues were reviewed from 100 pts who had undergone biopsy or radical prostatectomy for previously untreated advanced or metastatic PC from 2002 to 2007. 24 samples expressed hystologically chromogranin A (CgA), a marker of NED expression. Patient characteristics included: median age 68 years (range 45–83), median baseline PSA: 70 ng/ml (range 0.3–200), median ECOG Performance Status: 1 (range 0–2), Gleason score ≥ 7, medium serum level of CgA was 56.2 nmol/L (range 0.5–120). Results: The expression of SSTR subtypes (1, 2, 3, 4, 5) were investigated and our data identified four histological features. SSTR1 was expressed in 4/24 samples, SSTR 5 was detected in 2/24 samples, both SSTR1 and SSTR5 were found in 6/24 samples. OS at last follow up on July 2008 was 60%. SSTR 1–5 were undetectable in 12/24 pts with more aggressive clinical course and the OS was < 10%. The PSA and CgA levels were not correlated with clinical outcome. SSTR subtypes 2, 3 an 4 were not expressed in all 24 samples. Conclusions: SSTRs expression significantly correlated with OS. The absence of SSTR 1 and 5 in more aggressive disease could represent a growth advantage in NED prostate cancer. SSTRs and somatostatin analogs are potential targets for prostate cancer treatment. No significant financial relationships to disclose.

1032 poster MLN8054, A NOVEL INHIBITOR OF AURORA KINASE A SENSITIZES ANDROGEN-RESISTANT PROSTATE CANCER MODELS TO RADIATION

2011 ◽  
Vol 99 ◽  
pp. S386
Author(s):  
L. Moretti ◽  
K. Niermann ◽  
S. Schleicher ◽  
K.W. Kim ◽  
P. Kopsombut ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Aurora Kinase ◽  
Aurora Kinase A ◽  
Cancer Models ◽  
Kinase A

scholarly journals miR-199a-3p Inhibits Aurora Kinase A and Attenuates Prostate Cancer Growth

2014 ◽  
Vol 184 (5) ◽  
pp. 1541-1549 ◽  
Author(s):  
Yi Qu ◽  
Xiang Huang ◽  
Zhiqing Li ◽  
Junyan Liu ◽  
Jinlin Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Aurora Kinase ◽  
Cancer Growth ◽  
Aurora Kinase A ◽  
Kinase A

A phase II trial of the aurora kinase A inhibitor MLN8237 in patients with metastatic castrate resistant and neuroendocrine prostate cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS5096-TPS5096 ◽  
Author(s):  
Himisha Beltran ◽  
Mark A. Rubin ◽  
Juan Miguel Mosquera ◽  
Paul J. Christos ◽  
Olivera Calukovic ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Neuron Specific Enolase ◽  
Aurora Kinase ◽  
Response To Therapy ◽  
Aurora Kinase A ◽  
Kinase A

TPS5096 Background: NEPC can rarely arise de novo but more commonly arises as a mechanism of resistance in the setting of advanced prostate cancer. Transformation to NEPC is likely promoted by potent hormonal therapies and is currently under-recognized. There is no effective therapy for NEPC and most patients (pts) survive less than one year. We have found that Aurora kinase A (AURKA) and N-myc (MYCN) are significantly overexpressed and amplified in NEPC compared to prostate adenocarcinoma, and cooperate to induce neuroendocrine (NE) differentiation in prostate cancer (Beltran et al, Cancer Disc 2011). In preclinical models, aurora kinase inhibition results in dramatic and preferential anti-tumor activity in NEPC. Methods: In this single arm, multi-institutional Phase II trial, pts with metastatic prostate cancer need to meet at least one NEPC entry criterion: 1) histologic diagnosis of small cell or NEPC, 2) >50% immunohistochemical staining for NE markers, 3) development of liver metastases in absence of PSA progression, or 4) serum chromogranin >5x normal or neuron specific enolase >2x normal. Study will be open at 10 institutions including PCCTC sites. After a mandatory on-study research biopsy, pts will be treated with MLN8237, an orally administered Aurora kinase A inhibitor at 50 mg twice daily for 7 days repeated every 21 days. The primary endpoint is objective response rate (ORR). Secondary endpoints include overall survival, progression free survival, PSA response rate, circulating tumor cell response, and serum NE marker response to therapy. A number of correlative studies including AURKA, MYCN, AR, and exome and RNAseq are embedded in this trial in order to molecularly define this aggressive and poorly characterized disease. A Simon 2-stage design will be employed with up to 60 subjects providing 80% power to determine if the true ORR is >30% and 95% power if the true ORR is <15%, assuming a 5% level of significance. A subset of at least 20% meeting histologic entry criteria is embedded.

scholarly journals Effects of DNAzymes targeting Aurora kinase A on the growth of human prostate cancer

2008 ◽  
Vol 15 (8) ◽  
pp. 517-525 ◽  
Author(s):  
Y Qu ◽  
L Zhang ◽  
M Mao ◽  
F Zhao ◽  
X Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Aurora Kinase ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Aurora Kinase A ◽  
Kinase A

scholarly journals A phase 2 study of the aurora kinase A inhibitor alisertib for patients with neuroendocrine prostate cancer (NEPC)

2016 ◽  
Vol 27 ◽  
pp. vi565 ◽  
Author(s):  
H. Beltran ◽  
D. Danila ◽  
B. Montgomery ◽  
R. Szmulewitz ◽  
U. Vaishampayan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Aurora Kinase ◽  
Phase 2 ◽  
Aurora Kinase A ◽  
Neuroendocrine Prostate Cancer ◽  
Phase 2 Study ◽  
Kinase A
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