TREATING RESISTANCE TO HER-2 TARGETED THERAPY HAS NOW BEEN CLEARLY DEFINED.
In all evidence, the receptor resistance can be induced by change in shape, change in molecular content, and and change in molecular nature of product with which it interacts.  As it pertains to the Human Epidermal Growth factor Receptor or HER-2  Receptor, downstream interaction is with the PI3K/AKT/MTOR.
We now take it for granted as a truth that when,in a pathway, some thing clog the action, we target downstream steps.  If you can't stop the enemy in the street, or gate, try stop him at your doorstep.
So instead of stopping the Her-2 Receptor, inhibit the MTOR, mammalian target of Rapamycin!

So now inhibiting the MTOR is a strategy to stop resistance or add to the effect of target therapy aimed at HER-2.
and guess what, it works!  Proof of concept did materialize in clinical trials!  

Scientist now are also taking the Her-2 Receptor targeting molecule, attach it to a powerful chemotherapy molecule and send the whole thing into the cell (concept of T-DM1).

Trastuzumab emtansine

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Trastuzumab emtansine ^?

Monoclonal antibody
Type	Whole antibody
Source	Humanized (from mouse)
Clinical data
Trade names	Kadcyla
Pregnancy cat.	D (US)
Legal status	℞-only (US)
Routes	Intravenous infusion
Pharmacokinetic data
Bioavailability	N/A
Protein binding	93% (in vitro)
Metabolism	Hepatic (CYP3A4/3A5-mediated)
Half-life	4 days
Identifiers
CAS number	1018448-65-1
ATC code	None
UNII	SE2KH7T06F
KEGG	D09980
Chemical data
Formula	C6448H9948N1720O2012S44·(C47H62ClN4O13S)n
Mol. mass	148.5 kDa
(what is this?)  (verify)

Trastuzumab emtansine (INN;^[1][2] in the United States, ado-trastuzumab emtansine, trade name Kadcyla) is an antibody-drug conjugate consisting of the monoclonal antibody trastuzumab (Herceptin) linked to the cytotoxic agent mertansine (DM1).^[3][4][5][6] Trastuzumab alone stops growth of cancer cells by binding to the HER2/neu receptor, whereas mertansine enters cells and destroys them by binding to tubulin.^[7] Because the monoclonal antibody targets HER2, and HER2 is only over-expressed in cancer cells, the conjugate delivers the toxin specifically to tumor cells.^[8]
In the EMILIA clinical trial of women with advanced HER2 positive breast cancer who were already resistant to trastuzumab alone, it improved survival by 5.8 months compared to the combination of lapatinib and capecitabine.^[8] Based on that trial, the U.S. Food and Drug Administration (FDA) approved marketing on February 22, 2013.^[9][10][11]
Trastuzumab emtansine was developed by Genentech. The planned cost is expected to be $9,800 a month, or $94,000 for a typical course of treatment.<sup>[10] wikipidea.

ANOTHER STRATEGY CREATED BY SCIENTIST!</sup>

Pertuzumab

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Pertuzumab ^?

Monoclonal antibody
Type	Whole antibody
Source	Humanized (from mouse)
Target	HER2
Clinical data
Trade names	Perjeta; Omnitarg
Licence data	US FDA:link
Pregnancy cat.	D (US)
Legal status	℞-only (US)
Routes	Intravenous
Identifiers
CAS number	380610-27-5
ATC code	L01XC13
UNII	K16AIQ8CTM
KEGG	D05446
ChEMBL	CHEMBL2007641
Chemical data
Formula	?
(what is this?)  (verify)

The structure of HER2 and pertuzumab

Pertuzumab (also called 2C4, trade name Perjeta) is a monoclonal antibody. The first of its class in a line of agents called "HER dimerization inhibitors". By binding to HER2, it inhibits the dimerization of HER2 with other HER receptors, which is hypothesized to result in slowed tumor growth.^[1] Pertuzumab received US FDA approval for the treatment of HER2-positive metastatic breast cancer on June 8, 2012.^[2] Pertuzumab was developed at Genentech and is now owned by Roche which acquired Genentech in 2009.