new combination being studied--seems to reverse resistance which develops 2 heceptini

[Lani]

Breast Cancer Res Treat. 2008 Oct 14. [Epub ahead of print]

Lipid-conjugated telomerase template antagonists sensitize resistant HER2-positive breast cancer cells to trastuzumab.

Goldblatt EM, Erickson PA, Gentry ER, Gryaznov SM, Herbert BS.
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202-5251, USA.
HER2 amplification in breast cancer is associated with a more aggressive disease, greater likelihood of recurrence, and decreased survival compared to women with HER2-negative breast cancer. Trastuzumab is a monoclonal antibody that inhibits HER2 activity, making this compound an important therapeutic option for patients with HER2-positive breast cancer. However, resistance to trastuzumab develops rapidly in a large number of breast cancer patients. The objective of this study was to determine whether GRN163L, a telomerase template antagonist currently in clinical trials for cancer treatment, can augment the effects of trastuzumab in breast cancer cells with HER2 amplification. GRN163L was effective in inhibiting telomerase activity and shortening telomeres in HER2-positive breast cancer cells. We show that GRN163L acts synergistically with trastuzumab in inhibiting HER2-positive breast cancer cell growth. More importantly, we show that GRN163L can restore the sensitivity of therapeutic-resistant breast cancer cells to trastuzumab. These findings implicate that telomerase template antagonists have potential use in the treatment of cancers that have developed resistance to traditional cancer therapy.
PMID: 18853252 [PubMed - as supplied by publisher]

[Faith in Him]

Lani,

Would this be a benefit to those of us who may have switched receptors after being treated with herceptin? My inital dx was strongly her2+++ but my recurrence was not. I'm still on herceptin but not sure if it is doing me any good. Maybe receptors switching is another issue.

Thanks,
Tonya

[hutchibk]

It this in trials yet?

And, I love your new nickname... (typo?) - Herceptini - !! LOL. I currently imbibe in tri-weekly Herceptini's!

[Carolyns]

NCI TRIAL

http://www.cancer.gov/Templates/drugdictionary.aspx?CdrID=447136

[chrisy]

Now you're talkin! good to see research is going on to reverse resistance to our miracle drugs. Keep it coming and as brenda would say, hurry. Now I know it's just cause she likes her herceptin in a tini.

Thanks also, Carolyn, for the link to trials. Looks like it is not in trials yet with herceptin but hopefully this study will lead to that.

Thanks lani.

[StephN]

Chrisy -
At the American Association of Cancer Researchers annual meeting in April we met SO MANY researchers and academicians who were working on resistant tumors. Especially in the HER2 family. Some were working on exploring that problem with Herceptin and some even for Tykerb already.

So, with multiple researchers working in multiple centers in multiple countries, something is bound to happen soon.

They keep breaking down the cell structure and working with different components to find the reasons.

[Lani]

there is a lot of this which is not known.

It seems sometimes resistance may result from the cancer utilizing another signalling pathway to circumvent the blocking of another (sort of like the puppy sneaking out the back door when you lock the front door) and sometimes perhaps because other precursor cells now can outcompete the previously dominant cancerous cell type (like crabweed now taking over the lawn after you kill off the dandelions). Dr. Stephanie Jeffrey of Stanford has given a talk about phenotyping (identifying the molecular chaacteristics which typify) circulating tumor cells in her2 + breast cancer patients on herceptin.She reports they are extremely heterogeneous (off all sorts of types ie, E+, E-, her2+, her2-) and in fact reported triple negative ( ER-PR-her2-) circulating tumor cells ciculating in the blood of a patient with Stage IV her2+ breast cancer.

Discussions of the stem cell theory of breast cancer try to explain the origins of her2- metastases possible with her2+ breast cancer, but the answer is elusive and much about this remains controversial, it seems

Hope this helped somehow!

[Faith in Him]

Thank you, Lani. That was a better explanation than what I got from my onc. It helps me understand what may be going on.

Tonya