Okay, if you listened to the 2005 SABC live web cast with Gelbar speaking for the HERA trail, you would have noticed that at the end of that presentation, someone asked the relevance of tumor marker testing in relationship to determine herceptin response/resistane. Specifically, pTEN was mentioned as preclinically the presence of pTEN on one's tumor would indicate a much increased response to Herceptin. Gelbar indicated that they have the tissue specimens from the HERA trail and should be looking into testing for pTEN on those specimens. Wouldn't it be nice if they to see if the pre-clinical data correlates with actual human experience.
One other marker I hope they test for on the HERA trail specimens is TAB250 which tests for the extracellular membrane domain of her2. If you have the extracellar domain in tact with cleavage, Herceptin can bind to it and cellular proliferation events downregulate; thus, Herceptin is effective.Well, we certainly need more markers to test tumors in order to better define therapy and hopefully the HERA trail will deliver some of those results eventually.
Anyway, I had my tumor tested for these markers and had both so I figured it was worthwhile to do very late adjuvant Herceptin.I started it two days ago and it went well other than I hate needle sticks, being the baby I am. Thanks to everybody here that encouraged me along the way. Oh yeh, hopefully insurance will pay the bill for herceptin. We're going to submit it and see what happens. I am her2+ afterall very very strongly at 5.2 HER2-CEP ratio.
See the pasted article concerning pTEN's PRECLINICAL REVELANCE below:
Copyright © 2004 Cell Press.
Cancer Cell, Vol 6, 117-127, August 2004
PTEN activation contributes to tumor inhibition by trastuzumab, and loss of
PTEN predicts trastuzumab resistance in patients
Yoichi Nagata,
1,
6 Keng-Hsueh Lan,
1,
6 Xiaoyan Zhou,
1 Ming Tan,
1 Francisco J. Esteva,
2,
3 Aysegul A. Sahin,
4 Kristine S. Klos,
1 Ping Li,
1 Brett P. Monia,
5 Nina T. Nguyen,
1 Gabriel N. Hortobagyi,
2 Mien-Chie Hung,
3 and Dihua Yu
1,
3
1Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA
2Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA
3Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA
4Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA
5ISIS Pharmaceuticals, Carlsbad, CA 92008 USA
Correspondence:
The ErbB2-targeting antibody, trastuzumab (
Herceptin), has remarkable therapeutic efficacy in certain patients with ErbB2-overexpressing tumors. The overall trastuzumab response rate, however, is limited and what determines trastuzumab response is poorly understood. Here we report that
PTEN activation contributes to trastuzumab's antitumor activity. Trastuzumab treatment quickly increased
PTEN membrane localization and phosphatase activity by reducing
PTEN tyrosine phosphorylation via Src inhibition. Reducing
PTEN in breast cancer cells by antisense oligonucleotides conferred trastuzumab resistance in vitro and in vivo. Patients with
PTEN-deficient breast cancers had significantly poorer responses to trastuzumab-based therapy than those with normal
PTEN. Thus,
PTEN deficiency is a powerful predictor for trastuzumab resistance. Additionally, PI3K inhibitors rescued
PTEN loss-induced trastuzumab resistance, suggesting that PI3K-targeting therapies could overcome this resistance.
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