therapyresistant

Therapy-resistant is a term used to describe a condition that does not respond adequately to standard treatments that are commonly effective for that condition. It can describe a disease state that is present from the outset (intrinsic or primary resistance) or one that develops after an initial period of response (acquired or secondary resistance).

The concept applies across medical domains, including infectious disease, oncology, neurology, psychiatry, and pain management. Examples include antibiotic-resistant infections, tumors that do not respond to standard chemotherapy or targeted therapy, and mood or anxiety disorders that fail to improve with conventional pharmacotherapy or psychotherapy.

Causes and mechanisms of therapy resistance are diverse. They can involve pharmacokinetic factors such as poor absorption or rapid metabolism, pharmacodynamic changes like altered drug targets or receptor signaling, and disease-intrinsic features such as genetic or epigenetic heterogeneity. In cancer, mechanisms include clonal evolution, activation of compensatory pathways, drug efflux, and a protective tumor microenvironment. In infections, resistance arises through mutations or acquisition of resistance genes that reduce drug efficacy or enable drug inactivation.

Assessment typically includes verifying adherence and dosing, ruling out misdiagnosis or comorbidities, and using biomarkers or imaging to gauge response. Management often involves switching or adding therapies, combining modalities, optimizing dosing within safety limits, and exploring targeted or novel agents. In parallel, rehabilitation, psychosocial support, and consideration of clinical trials can play roles.

Ongoing research aims to understand resistance mechanisms, identify predictive biomarkers, and develop strategies to prevent or overcome therapy resistance, including personalized medicine and antimicrobial stewardship.