What is the Origin of Aromatase Inhibitor Resistance?

This term is firmly situated within the domain of clinical oncology and endocrinology, emerging from the widespread use of AIs like anastrozole, letrozole, and exemestane in the adjuvant and metastatic settings for estrogen-receptor-positive breast cancer. The phenomenon of resistance is a common biological principle in pharmacology, signifying a failure of the target cells to remain sensitive to the drug's mechanism of action.

What is the Mechanism of Aromatase Inhibitor Resistance?

Resistance often involves complex molecular and cellular changes that bypass the profound estrogen deprivation achieved by the AI. Potential mechanisms include upregulation of alternative growth factor signaling pathways, such as the PI3K/AKT/mTOR cascade, or mutations in the estrogen receptor itself, rendering the tumor estrogen-independent. Furthermore, altered pharmacokinetics or genetic polymorphisms affecting AI metabolism can also contribute to treatment failure, though true resistance is typically a tumor-intrinsic adaptation.

Aromatase Inhibitor Resistance ∞ Area

Aromatase Inhibitor Resistance

Meaning

A clinical state where hormone-receptor-positive breast cancer cells cease to respond effectively to treatment with aromatase inhibitors (AIs), leading to disease progression despite continued endocrine therapy. This acquired or de novo resistance represents a major challenge in long-term breast cancer management. Understanding the underlying cellular adaptations is crucial for developing subsequent therapeutic strategies.