I know that Herceptin is frequently used for treating breast cancer where HER2 is over expressed. I want to know whether we can use this antibody for treating other types of cancers as HER2 also over expressed in other cancers.
Mere expression of the protein is not the sufficient criteria to used as a drug target. One criteria for a protein to be used as a therapeutic target is its essentiality in the said tumor setting. One can target HER2 therapeutically only if it plays a dominant role in the proliferationa and survival of the said tumor.
Yes why not, herceptin is basically a monoclonal antibody targeting HER2 receptor, described first in chicken erytrhroblastic leukemia and was named as erbB2 and it shares homology with EGFR( also known as HER1).. Later on, it was found expressed in human breast cancer and named human epidermal growth factor receptor (HER)2. Since HER2 receptor is also expressed in human cervical, ovarian and gastric cancers, therefore, herceptin may be used in these cancers as adjuvant chemotherapy as well.
Are we talking here about preclinical or clinical studies?
What would be your hypothesis? The reason to use Herceptin is, exactly because it is overexpressed, if you find other cell lines / primary cells (never trust cell lines) which also have the receptor overexpressed, then you can run simple dose response assays like MTT / CCK8 or other proliferation assays and evaluate the sensitivity.
I would still recommend to you that you run a positive control with the a specific inhibitor for that particular cancer type / cell line, to evaluate how effective Hereceptin is.
For the case, you're interested in clinical studies (which only will work, if you have strong preclinical data), you should contact the regarding Pharma company (Roche). This would be their medical affairs department, btw.
Yes why not, herceptin is basically a monoclonal antibody targeting HER2 receptor, which was initially described in chicken erytrhroblastic leukemia and was named as erbB2. It shares homology with EGFR( also known as HER1).. Later on, it was found expressed in human breast cancer and named human epidermal growth factor receptor (HER)2. Since HER2 receptor is also expressed on human cervical, ovarian and gastric cancers, therefore, herceptin may also be used in these cancers as adjuvant chemotherapy.
Why not?
Herceptin has been approved by FDA for the treatment of Her2 positive gastric cancer. And some other clinical trials are going on.
Herceptin is an antibody with an extracellular epitope; if you think that it can reach and act on the everexpressed HER2 molecules, yes.
The problem is that HER2 can translocate upon overexpression(Ramsauer,VP et. al., 2003) to the apical surface of the cell. Thus, if this extracellular domain is now at the lumen side would herceptin be able to reach it?
The monoclonal antibody trastuzumab (Herceptin®), which may be used to treat breast and stomach cancer
I think there is some confusion. The HER2 receptor,and not the herceptin, has an extracellular domain which has a complex intracellular signaling mechanism leading to cell proliferation as one of the response. Herceptin, a monoclonal antibody raised against HER2 binds to epitope on this extracellular domain and thus blocks cell signaling by autocrine or paracrine loops
Therefore, on whichever type of cancer cell HER2 is expressed, herceptin will bind and thus block priliferation
If any tumour is positive for Her-2 yes it should work, but I know it is easier than done due to insurance issues. But where ever possible yes.
Have any body tried Herceptin on different cell lines and check sensivity of antibody. This may help in understanding genes other than HER2 responsible for drug sensitivity/resistance. Do we have expression profile of Herceptin resistant cell lines (or tissue) and Herceptin sensitive cell lines.
It has also been trialed for HER2-driven lung cancer.
http://clinicaltrials.gov/ct2/results?term=herceptin+her2+lung
Herceptin use for HER2 positive breast cancer and gastric cancer has been approved in many countries. In other type of cancer, I think, there are potential good candidates. However, randomized prospective study will be required.
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