Scientists Develop New Therapy For HER2-Positive Breast Cancer
Patients with HER2-positive breast cancer may soon have an alternative therapy when they develop resistance to trastuzumab, also known as Herceptin, according to a laboratory finding published in Clinical Cancer Research, a journal of the American Association for Cancer Research. Jacek Capala, Ph.D., D.Sc...
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Re: Scientists Develop New Therapy For HER2-Positive Breast Cancer
Bring it on! Let's hope it's in trials soon.
Ellie |
Re: Scientists Develop New Therapy For HER2-Positive Breast Cancer
Yeah. Define "Soon"
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Re: Scientists Develop New Therapy For HER2-Positive Breast Cancer
Great news! The concept was reported less than two years ago. Looks like they are making good progress. [See also Lani's thread: http://her2support.org/vbulletin/sho...ight=Affitoxin ]
J Immunother. 2009 Oct;32(8):817-25. Affitoxin--a novel recombinant, HER2-specific, anticancer agent for targeted therapy of HER2-positive tumors. Zielinski R, Lyakhov I, Jacobs A, Chertov O, Kramer-Marek G, Francella N, Stephen A, Fisher R, Blumenthal R, Capala J. Source Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Abstract Expression of the human epidermal growth factor receptor 2 (HER2) is amplified in 25% to 30% of breast cancers and has been associated with an unfavorable prognosis. Here we report the construction, purification, and characterization of Affitoxin-a novel class of HER2-specific cytotoxic molecules combining HER2-specific Affibody molecule as a targeting moiety and PE38KDEL, which is a truncated version of Pseudomonas exotoxin A, as a cell killing agent. It is highly soluble and does not require additional refolding, oxidation, or reduction steps during its purification. Using surface plasmon resonance technology and competitive binding assays, we have shown that Affitoxin binds specifically to HER2 with nanomolar affinity. We have also observed a high correlation between HER2 expression and retention of Affitoxin bound to the cell surface. Affitoxin binding and internalization is followed by Pseudomonas exotoxin A activity domain-mediated ADP-ribosylation of translation elongation factor 2 and, consequently, inhibition of protein synthesis as shown by protein expression analysis of HER2-positive cells treated with Affitoxin. Measured IC50 value for HER2-negative cells MDA-MB468 (65+/-2.63 pM) was more than 20 times higher than the value for low HER2 level-expressing MCF7 cells (2.56+/-0.1 pM), and almost 3 orders of magnitude higher for its HER2-overexpressing derivative MCF7/HER2 (62.7+/-5.9 fM). These studies suggest that Affitoxin is an attractive PE38-based candidate for treatment of HER2-positive tumors. |
Re: Scientists Develop New Therapy For HER2-Positive Breast Cancer
Hang in there Chrisy! Several new things have come available since you began this journey. I know the perfect combination is out there to push that cancer back! Any new drug gives everyone hope that their cure is just over the horizon. My prayers are with everyone that it is soon!
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Re: Scientists Develop New Therapy For HER2-Positive Breast Cancer
Hi Chrissy
Soon for me means within the next few months but I suspect it will take longer!! One thing that is becoming apparent is that there seems to be LOADS more promising agents coming onboard for her 2 than any other type. Cheers Ellie |
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