Insmed Inc (INSM)

[Christiaan F]

"This study only affected the MDA-MB231 cell line of breast cancers. IGFBP-3 is however highly effective against HER-2-positive breast tumors."

From Leyland-Jones Summary (confirms study result of November study):

The anti-tumour activity of rhIGFBP-3 against
ER+ MCF-7 human breast cancer xenografts was compared
to effects in ER- MDA-MB-231 xenografts [84].
Mice with established MDA-MB-231 tumours were
treated for three weeks with rhIGFBP-3, taxol or a combination
of the two agents. In contrast to the effects
noted in MCF-7, rhIGFBP-3 inhibited tumour growth
in MDA-MB-231 by up to 40% of control as a single
agent, but failed to show synergy with taxol. Furthermore,
Western blot analysis showed that rhIGFBP-3
treatment had differential effects on PI3K-AKT and
MAPK signalling in MCF-7 and MDA-MB-231 cells
[84].
Recombinant human IGFBP-3 was also examined
for activity against herceptin-resistant breast cancer sublines
(MCF-7/HER2-18, SKBR3/IGF-IR and BT474/
HerR) with elevated IGF-IR levels. Treatment with rhIGFBP-
3 resulted in dose-dependent growth inhibition of
breast cancer cells. Moreover, the rhIGFBP-3 elicited a
strong dose-dependent increase in herceptin sensitivity
of SKBR3/IGF-IR and BT474/HerR, but showed a less
marked effect with MCF-7/HER2-18 in vitro [85]. Subsequently,
a related in vivo study was undertaken to evaluate
the anti-tumour activity of rhIGFBP-3 in a
xenograft model of herceptin-resistant breast cancer.
Mice bearing HER-2-transfected (MCF-7/HER2-18)
human breast carcinomas were treated for 21 days with
either herceptin, rhIGFBP-3 or a combination of the
two agents. rhIGFBP-3 displayed potent single-agent
activity superior to that of herceptin alone and modest
combinatorial activity with it [86]. Our data strongly
indicate that IGFBP-3 exerts antiproliferative and proapoptotic
effects as demonstrated with in vitro and in vivo
models of human breast cancer and that its therapeutic
efficacy should be tested in clinical trials.

CF