Question 1

What is the Meaning of Androgen Receptor Splice Variants?

Accepted Answer

Androgen Receptor Splice Variants (AR-SVs) are distinct protein forms derived from the androgen receptor (AR) gene via alternative messenger RNA splicing. These variants typically lack the ligand-binding domain, yet retain capacity to activate gene transcription. Their presence reflects adaptive gene expression.

Question 2

What is the Context of Androgen Receptor Splice Variants?

Accepted Answer

These variants operate within the complex system of androgen signaling, particularly in hormone-sensitive tissues like the prostate. While the full-length AR mediates most physiological responses, AR-SVs can signal even without traditional androgen stimulation. This independent activity often emerges in disease, notably prostate cancer.

Question 3

What is the Significance of Androgen Receptor Splice Variants?

Accepted Answer

Clinically, AR-SVs hold importance, especially in prostate cancer management. Their presence, particularly AR-V7, correlates with resistance to androgen deprivation therapies and newer hormonal agents. Identifying these variants assists clinicians in predicting patient response, guiding decisions toward alternative therapeutic strategies.

Question 4

What is the Mechanism of Androgen Receptor Splice Variants?

Accepted Answer

Androgen receptor splice variants exert effects as constitutively active transcription factors. Unlike the full-length AR, which requires androgen binding for nuclear translocation, many AR-SVs are truncated, allowing nuclear localization and activation of target genes without ligand engagement. This bypasses regulatory controls, promoting cell proliferation.

Question 5

What is the Application of Androgen Receptor Splice Variants?

Accepted Answer

Detection of androgen receptor splice variants is increasingly applied in clinical oncology for metastatic castration-resistant prostate cancer. Liquid biopsy technologies, analyzing circulating tumor cells or cell-free DNA from blood, offer a non-invasive method for identification. This information helps personalize treatment, avoiding ineffective therapies and directing patients toward suitable options.

Question 6

What is the Metric of Androgen Receptor Splice Variants?

Accepted Answer

Measuring androgen receptor splice variants typically involves molecular diagnostic techniques. Quantitative polymerase chain reaction (qPCR) and next-generation sequencing (NGS) are common methods to detect and quantify specific AR-SV messenger RNA transcripts or protein levels. Samples frequently include circulating tumor cells from blood or tissue biopsies.

Question 7

What is the Risk of Androgen Receptor Splice Variants?

Accepted Answer

Relying on AR-SV status without comprehensive clinical assessment poses risks. Misinterpretation of test results, including false negatives or positives, could lead to suboptimal treatment. This might expose patients to unnecessary side effects or delay more beneficial therapies. Clinical decisions must integrate AR-SV data with the patient's complete clinical picture.

Androgen Receptor Splice Variants

Meaning

Context

Significance

Mechanism

Application

Metric

Risk

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