| Cellular and Biochemical Mechanisms | ||
| Decreased drug accumulation | ||
| Decreased drug influx | ||
| Increased drug efflux | ||
| Altered intracellular drug trafficking | ||
| Increased inactivation of drug or toxic intermediate | ||
| Increased repair of or tolerance to drug-induced damage to | ||
| DNA | ||
| Protein | ||
| Membranes | ||
| Decreased drug activation | ||
| Altered drug targets (quantitatively or qualitatively) | ||
| Altered co-factor or metabolite levels | ||
| Altered downstream effectors of cytotoxicity | ||
| Altered signaling pathway and/or apoptotic responses to drug insult | ||
| Altered gene expression | ||
| DNA mutation, amplification, or deletion | ||
| Altered transcription, posttranscription processing, or translation | ||
| Altered stability of macromolecules | ||
| In Vivo Mechanisms | ||
| Pharmacological and anatomic drug barriers (tumor sanctuaries) | ||
| Host-drug interactions | ||
| Increased drug inactivation by normal tissues | ||
| Decreased drug activation by normal tissues | ||
| Relatively increased normal tissue drug sensitivity (toxicity) | ||
From: Overview of Resistance to Systemic Therapy in Patients with Breast Cancer
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