scholarly journals Diversity in Androgen Receptor Action Among Treatment-naïve Prostate Cancers Is Reflected in Treatment Response Predictions and Molecular Subtypes

2020 ◽  
Vol 22 ◽  
pp. 34-44
Author(s):  
Salma Ben-Salem ◽  
Qiang Hu ◽  
Yang Liu ◽  
Mohammed Alshalalfa ◽  
Xin Zhao ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Treatment Response ◽  
Molecular Subtypes ◽  
Treatment Naïve ◽  
Receptor Action ◽  
Prostate Cancers

IDH1 mutation in prostate cancer: R132H and beyond.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 213-213 ◽  
Author(s):  
Amber Lea Flaherty ◽  
Jamie Teer ◽  
Jingsong Zhang
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Amino Acid ◽  
Brain Metastasis ◽  
Allele Frequency ◽  
Amino Acid Change ◽  
1000 Genomes ◽  
Primary Prostate Cancer ◽  
Treatment Naïve ◽  
Prostate Cancers

213 Background: Previous reports on mutations in the isocitrate dehydrogenase 1 (IDH1) gene in prostate cancer focused on the evolutionarily conserved residue R132 located in the substrate binding site of IDH1. One study reported R132 mutations in 2/75 (2.7%) prostate cancers, whereas the other study did not find R132 mutation in 4 prostate cancers. We therefore studied the IDH1 mutations in our prostate cancer targeted exon sequencing database. Methods: Targeted exon sequencing was performed on 52 treatment naïve prostate cancers as part of Moffitt Cancer Center’s Total Cancer Care initiative. The coverage was set to be at least 50 fold. 51/52 samples are primary prostate cancer obtained during radical prostatectomy and 1 sample is a brain metastasis. The 1000 Genomes and the NHLBI Exome Sequencing Project (ESP) were used to exclude likely polymorphisms. The catalogue of somatic mutations in cancer (COSMIC) was used to identify mutations seen in other sequencing projects, and Polyphen2 was used to predict the potential detrimental effect of the amino acid changes predicted from the genetic mutations. Results: 1/51 (2%) primary prostate cancers harbor the R132H mutation, which is known to generate the oncometabolite, (R)-2-hydroxylutarate. Y183C was identified in 1/51 samples. This amino acid change in exon 6 of IDH1 is seen at 1% allele frequency in 1000 Genomes and ESP-euro. It is classified as "probably_damaging" with a PolyPhen2 score of .999. Another "probably_damaging" amino acid change is T325M mutation, which is identified in a different primary prostate cancer. V178I in IDH1 was also identified and is thought to be an inherited variant, given it has an allele frequency of 4% in 1000 Genomes, 5% in ESP-european, and 8% in ESP-African-American. Among the frequent gene mutations in metastatic prostate cancer, only a missense mutation in the androgen receptor (H875Y) was identified in the treatment naïve brain metastasis. This H875Y has been linked to promiscuous androgen receptor. Conclusions: Mutations in IDH1 R132H and other “probably_damaging” amino acid changes are identified in primary prostate cancers. This holds further implications for future studies on prostate cancer, and may point to an interesting target in the disease.

scholarly journals Inflammatory Breast Cancer: Clinical Characteristics and Influence of Molecular Subtypes on Treatment Response

2021 ◽  
Vol 107 (1_suppl) ◽  
pp. 12-12
Author(s):  
D Aissaoui ◽  
M Bohli ◽  
R Ben Amor ◽  
J Yahyaoui ◽  
A Hamdoun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Response ◽  
Inflammatory Breast Cancer ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Luminal A ◽  
Her2 Positive ◽  
Luminal B ◽  
Significant Difference

Introduction: Inflammatory Breast Cancer (IBC) is a rare and very aggressive breast cancer with poor prognosis. The prevalence is different from a country to another. In Tunisia, it is about 5 to 7% of breast cancer. The aim of this study is to describe the epidemiological and histopathological features of patients with inflammatory breast cancer and to evaluate the treatment response according to the molecular subtypes. Methods: This retrospective review identified 31 patients with no metastatic IBC treated in our radiotherapy department between December 2019 and November 2020. IBC was confirmed using the clinical criteria. Baseline clinic-pathological and treatment information was retrieved from medical records. Statistical analysis was performed with IBM SPSS V.20. Results: Median age was 51.3 years [27-68]. 48% of tumors were grade 3. The average tumor size was 36mm [10-90]. The histological type was ductal carcinoma in 97%. Vascular invasion was noted in 24 patients (77%). Thirty patients were classified as stage IIIB and one patient was IIIC. 74% were hormone receptor positive and 45% were HER2 positive. Luminal B was the predominant subtype (52%) followed by Her2 positive (32%), Luminal A (23%), and triple negative (3%) All patients had chemotherapy: neoadjuvant for 26 patients (84%) and adjuvant for 5 patients (16%). Nine patients (29%) had tumor pathological complete response (pCR). Partial response was observed in 18 patients (58%). Lymph node pCR was noted in 16% of cases (n=5). Endocrine therapy and trastuzumab were given to 76% and 45% of patients, respectively. The influence of the molecular subtype was not statistically significant on the response to neoadjuvant treatment. The highest rate of pCR were 43% for Her2positive, then 27%, 21% and 9% for Luminal B, Luminal A and Triple negative, respectively (p=0.2). Conclusion: Our study showed a high percentage of hormone receptor and Her2+ (74% and 45% respectively) in IBC. Luminal B was the most frequent subtype. Anthracycline-based chemotherapy and trastuzumab improved the pCR rate: 44% for Her2positive. Triple negative showed poorer pCR than other breast cancer subtype without a significant difference. A larger study is warranted to confirm our findings.

scholarly journals Androgens and androgen receptor action in skin and hair follicles

2018 ◽  
Vol 465 ◽  
pp. 122-133 ◽  
Author(s):  
Julieta María Ceruti ◽  
Gustavo José Leirós ◽  
María Eugenia Balañá
Keyword(s):  
Androgen Receptor ◽  
Hair Follicles ◽  
Receptor Action

Molecular Biology Underlying the Clinical Heterogeneity of Prostate Cancer: An Update

2009 ◽  
Vol 133 (7) ◽  
pp. 1033-1040 ◽  
Author(s):  
A. Craig Mackinnon ◽  
Benjamin C. Yan ◽  
Loren J. Joseph ◽  
Hikmat A. Al-Ahmadie
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Molecular Biology ◽  
Gene Rearrangement ◽  
Molecular Characteristics ◽  
Early Event ◽  
Ablation Therapy ◽  
Androgen Ablation ◽  
Development Of Resistance ◽  
Prostate Cancers

Abstract Context.—Recent studies have uncovered a number of possible mechanisms by which prostate cancers can become resistant to systemic androgen deprivation, most involving androgen-independent reactivation of the androgen receptor. Genome-wide expression analysis with microarrays has identified a wide array of genes that are differentially expressed in metastatic prostate cancers compared to primary nonrecurrent tumors. Recently, recurrent gene fusions between TMPRSS2 and ETS family genes have been identified and extensively studied for their role in prostatic carcinoma. Objective.—To review the recent developments in the molecular biology of prostate cancer, including those pertaining to the androgen receptor and the newly identified TMPRSS2-related translocations. Data Sources.—Literature review and personal experience. Conclusions.—Prostatic adenocarcinoma is a heterogeneous group of neoplasms with a broad spectrum of pathologic and molecular characteristics and clinical behaviors. Numerous mechanisms contribute to the development of resistance to androgen ablation therapy, resulting in ligand-independent reactivation of the androgen receptor, including amplification, mutation, phosphorylation, and activation of coreceptors. Multiple translocations of members of the ETS oncogene family are present in approximately half of clinically localized prostate cancers. TMPRSS2:ERG gene rearrangement appears to be an early event in prostate cancer and is not observed in benign or hyperplastic prostatic epithelium. Duplication of TMPRSS2:ERG appears to predict a worse prognosis. The relationship between TMPRSS2:ERG gene rearrangement and other morphologic and prognostic parameters of prostate cancer is still unclear.

Hormonal therapy of prostate cancer

2011 ◽  
pp. 1622-1634
Author(s):  
Ciara O’Hanlon Brown ◽  
Jonathan Waxman
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Specific Antigen ◽  
Intraepithelial Neoplasia ◽  
Peripheral Zone ◽  
Molecular Feature ◽  
Molecular Defects ◽  
Psa Testing ◽  
Seer Data ◽  
Prostate Cancers

Prostate cancer is the most common cancer to effect men and the second most common cause of cancer-related death. Premalignant change or prostatic intraepithelial neoplasia has been detected within the prostate glands of men under 30 years of age. The incidence of prostate cancer remains negligible until men reach their 40s from whence it rises steadily and by 80 years 70% of men have detectable tumours at autopsy (1). A majority of prostate cancers arise from the peripheral zone of the prostate and rarely cause obstructive symptoms. Consequently, prostate cancers have historically presented late, with symptoms of metastatic disease. The advent of prostate-specific antigen (PSA) testing has produced a stage shift so that at present over 90% of prostate cancers are diagnosed as organ-confined disease. PSA diagnosis has unmasked a subset of prostate tumours that exhibit an indolent growth pattern and appear destined to remain organ-confined tumours the patient dies with, and not from. US SEER data estimates a 50-year-old man has a 42% chance of developing prostate cancer but only a 3.6% chance of dying from the disease. Features, either clinical or molecular, which would allow clinicians to clearly differentiate indolent from aggressive disease while still at the organ-confined stage, have yet to be identified (1). Adenocarcinoma is the predominant histological subtype of prostate cancer, accounting for 95% of tumours. Prostatic adenocarcinomas arise from androgen receptor-positive epithelial cells. On histological examination, prostate cancers appear multifocal and demonstrate heterogeneity both within individual tumours and across populations. This has created an obstacle as researchers attempt to subclassify prostate cancer and identify the molecular defects responsible for driving prostatic carcinogenesis (1). Of prostate cancers, 80–90% are androgen receptor-positive at diagnosis (2), thus to date the androgen–androgen receptor axis is the sole molecular feature of this disease that has been successfully harnessed as a therapeutic target.

scholarly journals Quantitative analysis of choroidal vasculature in polypoidal choroidal vasculopathy using ultra-widefield indocyanine green angiography

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Gahyung Ryu ◽  
Cheolwon Moon ◽  
Jano van Hemert ◽  
Min Sagong
Keyword(s):  
Indocyanine Green ◽  
Treatment Response ◽  
Polypoidal Choroidal Vasculopathy ◽  
Indocyanine Green Angiography ◽  
Vascular Density ◽  
Poor Treatment ◽  
Treatment Naïve ◽  
Healthy Control ◽  
Choroidal Vasculature ◽  
Choroidal Vasculopathy

Abstract Polypoidal choroidal vasculopathy (PCV) is a common choroidal vascular disease particularly in Asians. However, the underlying pathogenesis of PCV is still yet to be fully elucidated, and the correlation between choroidal vasculature and treatment response of PCV are poorly understood. Accordingly, we sought to find clues to understand the pathogenesis and prognosis of PCV by quantitatively evaluating choroidal vasculature from the entire fundus using ultra-widefield (UWF) indocyanine green angiography (ICGA). In this study, 32 eyes from 29 patients with treatment naïve PCV and 30 eyes from 30 healthy control participants were enrolled. Choroidal vascular density (CVD) of PCV eyes was higher than normal eyes in majority regions including the periphery. CVD was positively correlated with choroidal thickness and choroidal hyperpermeability, supporting that the pathogenesis of PCV may include choroidal congestion and dilatation. Thicker choroid and higher CVD were also correlated with poor treatment response after anti-VEGF injections. The CVD, quantified from UWF ICGA can also be used as an effective image biomarker to predict the treatment response in PCV.

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