Pertuzumab by Genentech

[julierene]

Pertuzumab: Directed against the HER2 family, pertuzumab is a humanized potential therapeutic antibody in Phase II testing. Pertuzumab is designed to directly attack tumor cell growth by inhibiting the signaling pathway of the entire family of HER kinases.

Future of Cancer Therapy and the HER Pathway Having established the HER pathway's role in a variety of solid tumors, molecular-targeted therapies are a valid and rationale approach to cancer treatment. Scientists are now utilizing the underlying biological mechanisms involved in cancer growth and metastases to develop clinical strategies to treat patients with cancer. While researchers continue to study the biological inner-workings of the HER pathway and other pathways involved in cancer, Genentech clinicians and collaborators are using the acquired knowledge to identify new and innovative ways to treat cancer patients.
Since certain receptors in the pathway work together to produce malignancy, one of the clinical strategies being explored today involves the possibility of combining several targeted HER molecules as well as other targeted therapies into a single treatment regimen - based on the biology of disease - that potentially have a synergistic or additive effect on the tumor and could on day lead to cancer becoming a more chronic disease.

http://www.gene.com/gene/products/education/oncology/herpathway.jsp

Could this be something even more powerful than Tykerb and Herceptin in the works?

[Joe]

Things are certainly looking good for Pertuzumab. Here are the results of a promising study:

http://cancerres.aacrjournals.org/cgi/content/full/64/7/2343

Regards
Joe

[Lani]

http://jnci.oxfordjournals.org/cgi/content/full/99/9/694
J Natl Cancer Inst. 2007 May 2;99(9):694-705. Links
Treatment of human epidermal growth factor receptor 2-overexpressing breast cancer xenografts with multiagent HER-targeted therapy.

Arpino G, Gutierrez C, Weiss H, Rimawi M, Massarweh S, Bharwani L, De Placido S, Osborne CK, Schiff R.
Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is a member of the HER signaling pathway. HER inhibitors partially block HER signaling and tumor growth in preclinical breast cancer models. We investigated whether blockade of all HER homo- and heterodimer pairs by combined treatment with several inhibitors could more effectively inhibit tumor growth in such models. METHODS: Mice carrying xenograft tumors of HER2-overexpressing MCF7/HER2-18 (HER2-transfected) or BT474 (HER2-amplified) cells were treated with estrogen supplementation or estrogen withdrawal, alone or combined with tamoxifen. One to three HER inhibitors (pertuzumab, trastuzumab, or gefitinib) could also be added (n > or = 8 mice per group). Tumor volumes, HER signaling, and tumor cell proliferation and apoptosis were assessed. Results were analyzed with the t test or Wilcoxon rank sum test and survival analysis methods. All statistical tests were two-sided. RESULTS: Median time to tumor progression was 21 days for mice receiving estrogen and 28 days for mice receiving estrogen and pertuzumab (difference = 7 days; P = .001; hazard ratio [HR] of progression in mice receiving estrogen and pertuzumab versus mice receiving estrogen = 0.27, 95% confidence interval [CI] = 0.09 to 0.77). Addition of gefitinib and trastuzumab to estrogen and pertuzumab increased this time to 49 days (difference = 21 days; P = .004; HR of progression = 0.28, 95% CI = 0.10 to 0.76). MCF7/HER2-18 tumors disappeared completely and did not progress (for > or = 189 days) after combination treatment with pertuzumab, trastuzumab, and gefitinib plus tamoxifen (19 of 20 mice) or plus estrogen withdrawal (14 of 15 mice). Both combination treatments induced apoptosis and blocked HER signaling and proliferation in tumor cells better than any single agent or dual combination. All BT474 tumors treated with pertuzumab, trastuzumab, and gefitinib disappeared rapidly, regardless of endocrine therapy, and no tumor progression was observed for 232 days. CONCLUSION: Combined treatment with gefitinib, trastuzumab, and pertuzumab to block signals from all HER homo- and heterodimers inhibited growth of HER2-overexpressing xenografts statistically significantly better than single agents and dual combinations.
PMID: 17470737 [PubMed - indexed for MEDLINE]

[alw]

Has anyone seen anything suggesting Pertuzumab is able to cross the Blood Brain Barrier?

My guess is that since it's a -mab and not a -nib - it would be too large. I'm not sure if that is correct.

Fondly,

Amy

[Lani]

to cross the blood brain barrier.

[hutchibk]

But remember - there is a small molecule Herceptin that Genetech is working on as well... I can't remember the post that refers to it, but I remember reading it and getting excited about it!

[chrisy]

Yes, all very promising.

As Brenda would say,

HURRY UP!

[Mary Anne in TX]

Is the new one the MC 1 thing? Oops, I mean the DM 1!
ma

[lilyecuadorian]

I wish to have the answer Mary Anne in TX ..before I go again and can ask the research oncology that is doing the research on this trial that I'm waiting to get ready I hope so is the same investigational drog !!!

[Lani]

As I understand it, the DM1 drug is even larger than herceptin because it is a herceptin antibody linked to a chemotherapy drug. It is not a pro-drug as I understand it (one in which the two parts of the combination are separated before the drug works, for example by processing in the liver)

So if you are looking for a "smaller herceptin" perhaps that is what you or someone else called a receptor tyrosine kinase inhibitor (like Tykerb) or an interfering RNA (none have yet been developed into drugs and unfortunately it looks like a while before they do) or perhaps something else altogether. Please let me know when you find the link you are referring to--maybe it is something I have missed altogether(very possible despite the volume of my reading)

[lilyecuadorian]

Thanks Lani