[Lani]

"nonresponse" to herceptin, but that is a hard thing to define. Does that mean 1)innate resistance, 2)acquired resistance or 3) just that another factor intervened which caused/allowe the patient's tumor to metastasize anyway.

elevated activated Akt could be a cause (even if herceptin stopped its activation, it could be activated on its own or via another pathway and result in the same endpoint)

biomarkers already known are , for example, low PTEN, or the inability of herceptin within the first few doses to decrease serum her2 ECD levels by ~20% (neither are absolute, but show a clear and significant trend in large numbers) The first two are examples of 1) and in the former case, might potentially also be a cuase of 2). Failure to block the ER and perhaps IGFR1
are said to be a cause of 2) and there are neoadjuvant studies by Spector, Bacus, et al to show that is the case with tykerb,also.

In the metastatic setting there is a 40% difference in the time required to "metabolize or clear" herceptin between those who do so slowly or quickly, so that could result in some failing herceptin because they just don't get it on the right schedule (that would fall in category 3)

So, as with everything else, it is not a simple picture like the RUBE GOLDBERG DIAGRAM I described yesterday. I have seen computer scientists at Stanford and Dr. Joel Gray at SABCS show diagrams of how they thing those parts of the network they know tie together with negative and positive feedback loops and the like and it would be an understatement to say it is a complicated picture. The reason to hope is that we now have very powerful computers working on the project. I think someone has posted how to donate one's computers "off time" toward finding a cure for cancer. Every
little thing helps!