ASCO new cheaper small molecule competitor to herceptin being developed

[Lani]

as a small molecule it might be possible to make it an oral medication...and if small enough, it might cross the blood-brain barrier:

Home > Abstracts & Virtual Meeting > Abstracts > 2007 ASCO Annual Meeting
In silico design of novel anticancer antibody mimetic molecules targeting HER2.
Sub-category:

Receptor-Targeted Antibodies/Ligands
Category:

Developmental Therapeutics: Molecular Therapeutics
Meeting:

2007 ASCO Annual Meeting


Abstract No:

14149
Citation:

Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 14149
Author(s):

H. Nakajima, S. Tanuma, I. Fujiwara, N. Mizuta, K. Sakaguchi
Abstract:

Background: HER2 is a unique receptor molecule for which no ligand has been found and functions as a coreceptor to form homo-and hetero-dimers with other three HER (1, 3 and 4) family members. The dimerization results in the activation of HER tyrosine kinase. This, in turn, promotes the tyrosine phosphorylation of certain proteins, leading to the stimulation of cell proliferation, invasion, and antiapoptosis. The overexpression of HER2 in breast cancer correlates with increased tumor growth and metastatic potential, and thereby poor long-term survival for the patient. A monoclonal antibody against HER2, named trastuzumab, is approved for breast cancer patients, while pertuzumab is currently in phaseIIclinical trial. The two antibodies bind to different epitopes in the extracellular domains of HER2. Trastuzumab binding mainly mediates the antibody-dependent cytotoxicity (ADCC). On the other hand, pertuzumab binding directly inhibits HER2 dimerization with its partner receptors, blocking the growth signaling and inducing apoptosis. Furthermore, the unique binding pockets on HER2 for trastuzumab and pertuzumab have been resolved and provide the important target domains for creation of new anticancer drugs. Methods: Based on these mechanisms, we are trying to design and create both antibodies-mimetic molecules using our in silico methodologies COSMOS (Conversion to small molecules through optimized-peptide strategy) and SARM (Self-assembling regulatory molecule). We design HRAP (HER2 reactive peptide)- SARM and HRAP- SARM- FAB (Fc?-binding peptide). HRAP-SARM may bind to HER2 pertuzumab binding site and sterically interferes with HER2 dimerization and induces apoptosis. HRAP- SARM- FAB is expected to induce both ADCC and apoptosis. Results and Conclusion: In this presentation, we will show the preliminary results and functions of the Ab-mimetics, HRAP-SARM and HRAP- SARM- FAB on human breast cancer cells overexpressing HER2, as compared to those of trastuzumab and pertuzumab. Since those Ab-mimetics are small molecules and cheap, the successful results are sure to promise the revolutionary therapy for refractory breast cancer.

[hutchibk]

I had read in the last couple of months about pertuzamab...

C'mon researchers! Git 'er done! This is great news.

[Adriana Mangus]

Where can I obtain the literature on this new drug?

Yes, it's great news.

Sending you positives vibes and a big HUG.

[LAURIE]

More hope on the way. Amazing!!! Where would we be without the research. Our spirit and voice will keep research like this in the forefront.

[Lani]

the above article is NOT about pertuzumab---it is another monoclonal antibody, a LARGE biological drug which will end up being expensive to produce. It is also being made by Genentech and is in Phase II trials and as its manufacture and distribution are likely to be as complicated as herceptin's, is likely to be expensive as wel.

This article is about making mimetic peptides, drugs which consist of short areas of protein which COPY (MIMIC) the most important stretches of the large molecules and DO THE SAME THING IN THE BODY, but are cheaper and easier to manufacture and able to cross the blood brain barrier They should also hopefully be less influenced by temperature(not need to stay within the same narrow temperature range as herceptin), hopefully more stable (herceptin has a short shelf-life once diluted) and perhaps be orally available (able to be taken as a pill)

[Adriana Mangus]

Lani:

But...there is a clinical trial Phase2 going on right now regarding the above -I would call it cousin of herceptin. Right? I was referring to that clinical trial, not the actual new drug being develope by Genentech. I asked Brenda for the article since she said she read something about it. I do understand the work the scientis are doing now that they now how these two drugs work together in the apoptosis of cancer cells for those who areHer2+.

Did I get it right this time, ?this is very complicated for a normal girl like us...

Praise the Lord we have you sister :-)

[Adriana Mangus]

Hi Brenda:

Do you remember where and how long you read about the above drug.
I'd appreciate a response.

[Lani]

I am the one who posted on "curing" her2+er+ breast cancer in mice with the combination of herceptin, pertuzumab and gefinitib (Iressa)

The abstract I posted from ASCO, however, is about small molecule peptides (building blocks of proteins) which are not yet in development. It is not research being done by Genentech.

We have Genentech to thank for Herceptin and pertuzumab (if it gets approved) and they have a drug similar to Iressa, called Tarceva, which is also a small molecule rather than a monoclonal antibody (which herceptin and pertuzumab are) It is for that reason that I am hopeful (it is hard to get different drug companies to work together to do a clinical trial involving products they don't all make)

The hopeful news about this abstract is
1) it may be possible that the new peptides cross the blood-brain barrier

2) they may be cheaper

3) perhaps they can be made with an easier formulation, stay effective longer in adverse conditions, etc so that some of those in the third world can reap the benefits those in the US and EU and Australia , Japan, etc take for granted since herceptin was approved.

Should the new drugs be cheaper, perhaps they won't "break the bank" of the nationalized health care services of various countries and won't leave those in countries with private health insurance with unaffordable premiums or uncovered.

[Kathy S in Tokyo]

I will ask my oncologist about the Ab-mimetics, HRAP-SARM and HRAP- SARM- FAB at my next consultation at the Tokyo National Cancer Center. He may know a little about it as he is very active in ongoing research and may know the authors of the abstract. I expect that he won't have much info in English about it yet unless colleagues from other countries are also researching it. It is definitely something to hope for; affordable and effective treatment.