Ad-mda7

does anyone know what this is? is this the link why some respond and others don't?

urgery. 2004 Aug;136(2):437-42. Related Articles, Links


Combination therapy of Ad-mda7 and trastuzumab increases cell death in Her-2/neu-overexpressing breast cancer cells.

McKenzie T, Liu Y, Fanale M, Swisher SG, Chada S, Hunt KK.

Department of Surgical Oncology, Division of Medicine, the University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

BACKGROUND: Overexpression of the tumor suppressor gene melanoma differentiation-associated gene-7 (mda-7) induces apoptosis in many cancer cells, and adenoviral-mediated overexpression of mda-7 downregulates beta-catenin and PI 3-kinase signaling in breast cancer cells. Trastuzumab (Herceptin) improves the efficacy of chemotherapeutics against Her-2/neu-overexpressing breast cancer cells. We sought to evaluate the impact of combination therapy of a recombinant adenovirus vector encoding for human mda-7 (Ad-mda7) and Herceptin on Her-2/neu-overexpressing breast cancer. METHODS: The MCF-7-Her-18 cell line was subjected to treatment with Ad-mda7 with and without Herceptin. Western blot analysis was performed with antibodies to beta-catenin, Akt, and phosphorylated Akt (p-Akt). The same treatment groups were utilized in a nude mouse model in vivo. Treatment was initiated when the tumors reached 100 mm3 in size. RESULTS: In Western blotting, the combination of Ad-mda7 + Herceptin showed decreased levels of beta-catenin, Akt and p-Akt compared with Ad-mda7 or Herceptin alone (P < .05). The in vivo analysis revealed a marked decrease in tumor size with the Ad-mda7 + Herceptin combination (P < .05). CONCLUSIONS: These studies demonstrate the growth inhibitory effect of Ad-mda7 + Herceptin on Her-2/neu-overexpressing breast cancer cells in vitro and in vivo. This combination appears to inhibit the pathways involving beta-catenin and Akt, which play important roles in the growth of breast cancer cells. Copyright 2004 Elsevier Inc

[StephN]

Hi -
Interesting - I have never heard of the mda-7 (melanoma differentiation associated gene) having anything to do with breast cancer or Her2. Maybe they are looking for some correlation with growth of melanoma and Her2 positive cell growth and/or suppression?

Looks like some ground breaking research.

Hi Kristen,

This is an interesting article. I think this is somewhat like a combo of vaccine and Herceptin. They have targed a virus against beta-catenin and combined it with Herceptin. Did you see if they were going to have any further trials with this stuff. I would be curious to see what they come up with. Thanks for sharing the article. ANNE

Hi Kristen,
I found some infor on this. Introgen seems to be the company spear-heading this. They make a P35 Vaccine called Advexin which is in phase 3 trials and oncolytic virus INGN 241, which seems to be the targetting therapy you refer to.
This seems to be in phase 2 trials:

http://www.leaddiscovery.co.uk/target-disc...Med-120405.html


also, http://www.medicalnewsservice.com/ARCHIVE/MNS2236.cfm

And here is an article with herceptin:

http://www.prnewswire.com/cgi-bin/stories....02238556&EDATE=
I have put a call into Introgen about the trials and will post back when I receive an answer.

The thing about these highly targetted therapies, is that they target a very narrow range of proteins, some of which our personal cancers may respond to, others not. That what makes this disease so complicated. However, anything that targets HER2 is a good thing!
Al

Thank you all for the information you posted. I really appreciate it. K
ps Al, let us know what you find out. TY

Kristen,
I haven't heard back from these guys yet so I called them again today and was assured that I would get a response within 24 hours. Linda has Chemo tomorrrow so I may miss the call but will post when I find-out more.
Al

Thanks Al,
Give my best to Linda. Take Care K