therapeutic resistance
The development of insensitivity to cancer treatment, either present initially (primary resistance) or acquired during therapy (secondary resistance), often involving new genetic alterations.
Full Definition
Therapeutic resistance refers to a tumor's ability to survive and progress despite treatment with targeted therapies, chemotherapy, or immunotherapy. Primary (intrinsic) resistance exists from treatment initiation due to pre-existing genetic alterations or tumor characteristics that prevent drug effectiveness. Secondary (acquired) resistance develops during treatment through new mutations, alternative pathway activation, or clonal evolution that allows cancer cells to escape therapeutic pressure. Common resistance mechanisms include bypass signaling, target modification, drug efflux pumps, and epithelial-mesenchymal transition. Understanding resistance patterns is crucial for treatment sequencing and combination therapy strategies. Molecular monitoring can sometimes detect emerging resistance before clinical progression occurs.
Usage
Usage note: Distinguish between primary (intrinsic) and secondary (acquired) resistance; specify mechanism when known.
In Context
- "Secondary therapeutic resistance emerged after 14 months of targeted therapy due to a T790M mutation." — Treatment monitoring report
- "Primary therapeutic resistance to EGFR inhibitors was attributed to concurrent KRAS mutation." — Molecular profiling interpretation