Question 1

What is the Meaning of F877L Mutation?

Accepted Answer

The F877L mutation represents an amino acid substitution where Phenylalanine (F) at position 877 is replaced by Leucine (L). This alteration is recognized in the ligand-binding domain of the androgen receptor, a key protein in hormonal signaling. Such a precise molecular change can significantly impact protein function and cellular responses.

Question 2

What is the Context of F877L Mutation?

Accepted Answer

This genetic alteration occurs within the gene encoding the androgen receptor (AR), a nuclear receptor protein mediating physiological actions of androgens like testosterone. The AR is widely expressed, playing a vital role in male sexual development, prostate growth, and maintaining bone and muscle mass. Its proper function is essential for normal endocrine system regulation.

Question 3

What is the Significance of F877L Mutation?

Accepted Answer

Clinically, the F877L mutation holds considerable importance, especially in prostate cancer management. Its presence can indicate resistance to certain anti-androgen therapies, affecting treatment efficacy and patient prognosis. Understanding this specific mutation helps clinicians tailor therapeutic strategies, potentially guiding decisions towards alternative interventions to improve patient outcomes.

Question 4

What is the Mechanism of F877L Mutation?

Accepted Answer

The F877L substitution in the androgen receptor's ligand-binding domain modifies its three-dimensional structure. This conformational change can alter the receptor's affinity for natural ligands and therapeutic anti-androgens. Consequently, the mutated receptor may exhibit promiscuous binding to non-androgenic steroids or facilitate constitutive activity, leading to sustained pro-growth signaling in androgen-depleted environments.

Question 5

What is the Application of F877L Mutation?

Accepted Answer

In clinical practice, identifying the F877L mutation is critical for guiding treatment decisions in patients with castration-resistant prostate cancer (CRPC). Its detection often signals reduced sensitivity to second-generation anti-androgens like enzalutamide, prompting consideration of alternative systemic therapies. Molecular profiling for this mutation assists oncologists in optimizing personalized therapeutic regimens.

Question 6

What is the Metric of F877L Mutation?

Accepted Answer

The F877L mutation's presence is typically determined through molecular diagnostic techniques. Genetic sequencing, including next-generation sequencing (NGS) or Sanger sequencing, is performed on DNA from tumor tissue biopsies or liquid biopsies, containing circulating tumor DNA (ctDNA). Monitoring mutation status over time can provide insights into disease progression and treatment response.

Question 7

What is the Risk of F877L Mutation?

Accepted Answer

Failure to recognize the F877L mutation in a patient with progressive prostate cancer can lead to continued administration of ineffective anti-androgen therapies, resulting in delayed disease control and potential worsening of symptoms. This mismanagement exposes patients to unnecessary side effects of treatments unlikely to provide benefit, ultimately compromising their well-being and clinical course.

F877L Mutation

Meaning

Context

Significance

Mechanism

Application

Metric

Risk

How Do Androgen Receptor Mutations Affect Treatment Outcomes?