Question 1

What is the Meaning of W742C Mutation?

Accepted Answer

The W742C Mutation is a highly specific point mutation within the ligand-binding domain of the Androgen Receptor (AR), where the amino acid Tryptophan at position 742 is replaced by Cysteine. This genetic alteration is clinically significant as it is frequently identified in advanced, castration-resistant prostate cancer (CRPC). The mutation fundamentally alters the receptor's structure, causing it to respond paradoxically to certain anti-androgen drugs.

Question 2

What is the Origin of W742C Mutation?

Accepted Answer

This mutation was discovered through molecular oncology and endocrinology research focused on mechanisms of drug resistance in prostate cancer patients receiving anti-androgen therapy. The nomenclature, W742C, is standard for single-amino-acid substitutions, indicating the original amino acid (W for Tryptophan), its position (742), and the new amino acid (C for Cysteine). Its origin marks a breakthrough in understanding hormonal resistance at the molecular level.

Question 3

What is the Mechanism of W742C Mutation?

Accepted Answer

The core mechanism of the W742C mutation is its ability to convert anti-androgen drugs, which are designed to block the AR, into agonists that actually activate the receptor. The structural change in the ligand-binding pocket allows the anti-androgen molecule to fit in a way that induces a conformational change necessary for gene transcription. This results in the drug inadvertently fueling cancer cell growth, leading to treatment failure and a state known as anti-androgen withdrawal syndrome.

W742C Mutation

Meaning

Origin

Mechanism

How Do Androgen Receptor Mutations Affect Treatment Outcomes?

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