Direct inhibition of PI3K in combination with dual HER2 inhibitors is required for optimal antitumor activity in HER2+ breast cancer cells

Table 1 Mean half-maximal inhibitory concentrations for lapatinib inhibition of HER2 and signaling proteins in PIK3CA mutant cells ^a

	HER2	Akt	Increase over WT	S6	Increase over WT
BT474	0.0411	0.0300		0.0347
BT474 LR	0.0204	0.3925	13.1	0.7863	22.7
BT474 wt	0.0798	0.0387		0.0506
BT474 E545K	0.0852	0.1098	2.8	0.1251	2.5
BT474 H1047R	0.0978	0.1336	3.4	0.1829	3.6
SKBR3	0.0254	0.0077		0.0106
SKBR3 wt	0.0297	0.0293		0.0593
SKBR3 E545K	0.0211	0.0936	3.2	0.1563	2.6
SKBR3 H1047R	0.0241	0.0770	2.6	0.2028	3.4
MDA361	0.0160	0.0092	0.5	0.0354	1.6
HCC1954	0.0681	0.2527	13.4	0.1678	7.4
SUM190	0.0465	0.0464	2.5	0.1461	6.5
UACC893	0.0444	0.2920	15.5	4.0040	177.0

^aWT, Wild type. Half-maximal inhibitory concentration (IC₅₀) values for inhibition of HER2, Akt and S6 phosphorylation by lapatinib treatment were determined by enzyme-linked immunosorbent assay (dose–response curves are shown in Additional file 6: Figure S2, Additional file 7: Figure S3 and Additional file 8: Figure S4). Mean IC₅₀ values derived from at least three separate experiments are shown. For phosphoinositide 3-kinase signaling proteins Akt and S6, IC₅₀ values from cells with PIK3CA mutations were compared to average values for cells without hotspot mutations (BT474 and SKBR3).

ISSN: 1465-542X