Is prevention of her2+ brain mets around the corner? Oral TKI Pazopanib

[Lani]

(a tyrosine kinase inhibitor like lapatinib) holds promise to do just that!

Am J Pathol. 2013 Apr 11. pii: S0002-9440(13)00222-8. doi: 10.1016/j.ajpath.2013.02.043. [Epub ahead of print]
Pazopanib Inhibits the Activation of PDGFRβ-Expressing Astrocytes in the Brain Metastatic Microenvironment of Breast Cancer Cells.
Gril B, Palmieri D, Qian Y, Anwar T, Liewehr DJ, Steinberg SM, Andreu Z, Masana D, Fernández P, Steeg PS, Vidal-Vanaclocha F.
Source
Women's Cancers Section, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. Electronic address: grilbrun@mail.nih.gov.
Abstract
Brain metastases of breast cancer occur in more than one-third of metastatic breast cancer patients whose tumors overexpress HER2 or are triple negative. Brain colonization of cancer cells occurs in a unique environment, containing microglia, oligodendrocytes, astrocytes, and neurons. Although a neuroinflammatory response has been documented in brain metastasis, its contribution to cancer progression and therapy remains poorly understood. Using an experimental brain metastasis model of breast cancer, we characterized the brain metastatic microenvironment of brain tropic, HER2-transfected MDA-MB-231 human breast carcinoma cells (231-BR-HER2). A previously unidentified subpopulation of metastasis-associated astrocytes expressing phosphorylated platelet-derived growth factor receptor β (at tyrosine 751; p751-PDGFRβ) was identified around perivascular brain micrometastases. This subpopulation of p751-PDGFRβ+ astrocytes was also identified in human brain metastases from eight different craniotomy specimens and in primary cultures of astrocyte-enriched glial cells. Previously, we reported that pazopanib, a multispecific tyrosine kinase inhibitor, prevented the outgrowth of 231-BR-HER2 large brain metastases by 73%. Here, we evaluated the effect of pazopanib on the brain neuroinflammatory microenvironment. Pazopanib treatment resulted in 70% (P = 0.023) decrease of the p751-PDGFRβ+ astrocyte population, at the lowest dose of 30 mg/kg, twice daily. Collectively, the data identify a new subpopulation of activated astrocytes in the subclinical perivascular stage of brain metastases and show that they are inhibitable by pazopanib, suggesting its potential to prevent the development of subclinical perivascular micrometastases in breast cancer patients.
Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
PMID: 23583652 [PubMed - as supplied by publisher]

[dchips1]

Thanks for always posting the newest and latest, and your devotion to helping others.

Darita

[Ellie F]

Thanks Lani
Good to read this research. Is pazopanib available in the States already for other uses?
Ellie

[conomyself]

http://en.wikipedia.org/wiki/Pazopanib

According to this, it is being used for other types of cancers...

Rachael

[Midwest Alice]

Thanks Lani, I think I'll show this to my Onc

['lizbeth]

So . . . along these lines. What do you think the repercussions are of occasionally taking 25 to 50mg of L-tyrosine?

I find since cancer treatment my cognitive function improves with a small amount of L-tyrosine (dopamine), Lecithin (for aceytlcholine) and L-Glutamine (GABA).

I take Lecithin 3 - 5 times per week, and the others when I am trying to learn new information for work or school.

The supplements make a huge difference when I'm being challenged with new information or need to recall previous learning.

Has anyone seen any research on these specific supplements and Her2+ cancer?

[Lani]

It has been approved for renal cell carcinoma and soft tissue sarcoma by the U.S. Food and Drug Administration.

Thus it would only be "off-label use"

Please note, I am not saying this has been shown definitively to prevent her2+ brain mets while being both safe and efficacious. I am saying it is looking like it might turn out to help prevent her2+ brain mets and that if prospective blinded clinical trials show it to be(and that is still a big IF) , it shouldn't take too long to be approved as it is already approved for other indications.

[dearjilly]

Yes Alice, me too. Thanks Lani! Good news here!