HER2 Support Group Forums - View Single Post - I strongly recommend you read this article (even if you have to struggle a bit)

Lani · 06-22-2012, 11:23 AM

No, we don't even know if this drug is safe and effective in humans yet.

But the great news is for the first time they have what seems like a reasonable model of metastatic her2+ breast cancer--it is the metastases that kill, not the primary tumor. And they have a drug which crosses the blood brain barrier.

They may find they have to combine say herceptin, TDM-1 and/or pertuzumab with a PI3K inhibitor (as it is the PI3K pathway which often is responsible for antiher2 therapy resistance). For some it may end up being herceptin, TDM-1 and/or pertuzumab plus a Hsp90 inhibitor or plus an mTor inhibitor. But we have drugs in all these classes either in Stage II/III trials or already approved and now a way to see in real time and using human tumors (and in some cases the patients own immune system transplanted into the same mice) what works in what cases.

Again, I still feel serial bone marrow will also be helpful in this pursuit, but
this is a great leap forward in finding out how her2+ breast cancer develops (perhaps it takes both mutations AND loss/loss of function of B,T, and NK cells), how to best treat each of its subtypes, how to block its usual modes of escape and how to correctly dose and how long to treat with these agents.

This is really different from the NodSCID mice they have used before and the her2 transfected cell lines (extremely artificial constructs which may in no way behave like the real thing).

I expect it will speed things up remarkably--at least I hope so!

06-22-2012, 11:23 AM	#3
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	Re: I strongly recommend you read this article (even if you have to struggle a bit) No, we don't even know if this drug is safe and effective in humans yet. But the great news is for the first time they have what seems like a reasonable model of metastatic her2+ breast cancer--it is the metastases that kill, not the primary tumor. And they have a drug which crosses the blood brain barrier. They may find they have to combine say herceptin, TDM-1 and/or pertuzumab with a PI3K inhibitor (as it is the PI3K pathway which often is responsible for antiher2 therapy resistance). For some it may end up being herceptin, TDM-1 and/or pertuzumab plus a Hsp90 inhibitor or plus an mTor inhibitor. But we have drugs in all these classes either in Stage II/III trials or already approved and now a way to see in real time and using human tumors (and in some cases the patients own immune system transplanted into the same mice) what works in what cases. Again, I still feel serial bone marrow will also be helpful in this pursuit, but this is a great leap forward in finding out how her2+ breast cancer develops (perhaps it takes both mutations AND loss/loss of function of B,T, and NK cells), how to best treat each of its subtypes, how to block its usual modes of escape and how to correctly dose and how long to treat with these agents. This is really different from the NodSCID mice they have used before and the her2 transfected cell lines (extremely artificial constructs which may in no way behave like the real thing). I expect it will speed things up remarkably--at least I hope so!