Introduction
Materials and methods
Reagents and cell culture
Establishment of resistant cell lines
siRNA in 2D/3D
Protein extraction and immunoblot
Apoptosis and proliferation assays
Quantification of 3D cultures
Statistical considerations
Results
The β1 integrin's downstream kinases FAK and Src are activated upon acquisition of resistance to lapatinib-containing HER2-targeted therapies
β1 inhibition overcomes L resistance in ER+, HER2-amplified BT474 cells
Cell line | Drug → | Lapatinib | Trastuzumab | LT |
---|---|---|---|---|
Derivative | % Inhibition (95% CI) | % Inhibition (95% CI) | % Inhibition (95% CI) | |
BT474
|
Parental
| 100.0% | 72.1% (67.6%, 76.0%) | 100.0% |
Resistant
| 5.7% (-0.3%, 11.4%) | 11.4% (5.8%, 16.8%) | 13.7% (8.6%, 18.6%) | |
HCC1954
|
Parental
| --- | 7.4% (3.8%, 10.9%) | 100.0% |
Resistant
| --- | 5.4% (1.4%, 9.2%) | 37.8% (32.5%, 42.7%) |