Publications by authors named "Julie Lockman"
Tumors residing in the central nervous system (CNS) compromise the blood-brain barrier (BBB) via increased vascular permeability, with the magnitude of changes dependent on the tumor type and location. Current studies determine penetrability of a cancer therapeutic by administering progressively larger molecules until cutoff is observed where little to no tumor accumulation occurs. However, decades-old experimental work and mathematical modeling document methods to calculate both the size of the vascular opening (pore) with solute permeability values.
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- The blood-brain barrier (BBB) protects the brain by preventing many substances from entering, using tight junctions and efflux transporters like P-glycoprotein (P-gp) to regulate what can pass through.
- In brain metastases, the blood-tumor barrier (BTB) allows greater permeability but it's unclear how well P-gp functions in this compromised state.
- Research in a mouse model shows that P-gp levels and activity at the BTB are comparable to the BBB, indicating that despite changes in integrity, efflux mechanisms like P-gp might still hinder drug delivery to brain tumors.
Purpose: Lapatinib, a small molecule EGFR/HER2 inhibitor, partially inhibits the outgrowth of HER2+ brain metastases in preclinical models and in a subset of CNS lesions in clinical trials of HER2+ breast cancer. We investigated the ability of lapatinib to reach therapeutic concentrations in the CNS following (14)C-lapatinib administration (100 mg/kg p.o.
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