|
04-16-2013, 04:15 PM
|
#1
|
Senior Member
Join Date: Mar 2006
Posts: 4,778
|
Is prevention of her2+ brain mets around the corner? Oral TKI Pazopanib
(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]
|
|
|
04-16-2013, 09:17 PM
|
#2
|
Senior Member
Join Date: May 2006
Location: Mesa, Az
Posts: 219
|
Re: Is prevention of her2+ brain mets around the corner? Oral TKI Pazopanib
Thanks for always posting the newest and latest, and your devotion to helping others.
Darita
__________________
dx 1/06 IDC 2cm 38 at dx
2/06 L mast nodes 3/9+ SNB neg ER-/Pr - her2 + Stg 4 liver/pelvis
3/06-9/06Taxol/Carbo/zometa/Herceptin
3/07 6 brain mets WBR down to c-2
4/07 osteonecrosis jaw
1/08 mri new 9mm lesion right lower side
2/08 gamma knife 1 lesion 11/08 regamma
10/09 latent rad necrosis to brain met,
1/20/10 crani: lesion necrosis w active cells continue her add tykerb
1/11 NED just Ingrown toenail! YEAH GOD
8/11 Tykerb, herceptin weekly, elevated her2 levels, negative scans
oct -march 11 new neuro deficits lower legs
3/12 2 spinal metsTykerb, Herceptin
04/12 4050cGY rads T 2-4 & T7-9
5/12 Brain,cervical lumbar clear/thoracic slight decrease
10/12 t 2-4 shrunk t-9 grew start Xeloda, 02/13 stop xeloda,5/13 on metformin, decadron, Tykerb, iv and IT herceptin 5/30/13 total #11 #2 of 80mg dose weekly.
9/13 100mg of IT her, IV hern, 750 mg tykerb, 3mg dec.
last Mri T--3 SHRUNK t7-9 shrunk no edema. Left shift in CBC bone marrow BX negative.
10/13 Ct has shown Double left ureters with stones/cysts in them, after 3 births and lots and U/S iit takes cancer to figure out you have 2 smaller ureters going into 1 kidney!
12/13 Mri brain no new lesions, cervical and lumbar arthritis.
Tspine lesion at T3 stable, T 7-9 GROWTH lots of pain
1/29/14 HIHO HIHO its off to Neuro surgery I go
Life is Good when you wake up in the morning and take a breath and know that God has given me another day.
|
|
|
04-17-2013, 04:32 AM
|
#3
|
Senior Member
Join Date: Feb 2009
Posts: 1,526
|
Re: Is prevention of her2+ brain mets around the corner? Oral TKI Pazopanib
Thanks Lani
Good to read this research. Is pazopanib available in the States already for other uses?
Ellie
|
|
|
04-17-2013, 11:56 AM
|
#4
|
Senior Member
Join Date: Sep 2012
Posts: 111
|
Re: Is prevention of her2+ brain mets around the corner? Oral TKI Pazopanib
http://en.wikipedia.org/wiki/Pazopanib
According to this, it is being used for other types of cancers...
Rachael
__________________
7/30/2012 Diagnosed with metastatic breast cancer
8/3/2012 CT scan mets to liver (major!!), lungs, spine, and skin
8/8/2012 Biopsy results: invasive ductal carcinoma
ER+/PR+/HER2+ amplification 4.8 (whatever that means)
8/13/2012 Brain MRI (clear); bone scan verified CT scan
8/14/12 started Taxotere/Carboplatin/Herceptin, 2 rounds (added Neulasta after 9/4 treatment)
9/4/12 CA 15-3: >3000
9/15/12 CA 15-3: 840
9/15/12 started Taxotere/Perjeta/Herceptin, 4 rounds (no Neulasta)
10/29/12 CT scan showed dramatic improvement in all areas - largest liver met 2.5 cm, largest lung met 10 cm
12/17/12 Started Perjeta/Herceptin, 2 rounds
12/17/12 CA 15-3: 17 Yay!!!
1/21/13 CT scan showed improvement - largest liver met 1.9 cm, largest lung met 2 mm
1/29/13 CA 15-3: 12 Started Herceptin only
3/12/13 CA 15-3: still 12 yay!! Back to Perjeta/Herceptin
3/29/13 CT scan more improvement - largest liver met 1.2 cm, some lung mets disappeared!
3/7/14 started Tamoxifen
6/27/13 - 1/2015 CT scan stable
Began a diet of only single ingredient foods and went nearly NED excepts for some tiny lung spots - ask me if you want to know more...
1/2015 - 1/2017 CT scan stable
|
|
|
04-17-2013, 06:48 PM
|
#5
|
Senior Member
Join Date: Dec 2008
Location: Southern Indiana
Posts: 455
|
Re: Is prevention of her2+ brain mets around the corner? Oral TKI Pazopanib
Thanks Lani, I think I'll show this to my Onc
__________________
Alice
04/08 age 50 III IBC Her2+++ ER/PR-8cm 14/14 Double M, Body and Brain CT/PET clear, ? on spine,Muga 53
06/08, 4 A/C, Neulasta
08/08, Herceptin/tax 12 every week
10/08, CT/PET clear, ? on pelvis, hips, MUGA 43, started Enalaprial for heart, Herceptin every 3 weeks
11/08 33Rads; 12/08 MUGA 48
2/09 MRI spine and bone scan, old mets to spine, Chest x-ray, blood work, IV NED,regular CPAP use,Zometa x6, first -flue like symptoms 2 days;Herceptin x3; stage 2 lymphoedema..sleeve and glove
4/09 Brain MRI - CLEAR; MUGA 54
7/09 chest ultrasound,
10/09 PET, brain and spin MRI NED Herceptin only. MUGA 59!!!
1/11 Hip replacement 7/11 Hip 2 replacement
4/12 4 years!! Herceptin
6/12 start reconstruction finish in 12/12
2/14 Herception - 6 years!!!
1 Corinthians 10:13 "No temptation has seized you except what is common to man. And God is faithful; he will not let you be tempted beyond what you can bear. But when you are tempted, he will also provide a way out so that you
can stand up under it."
|
|
|
04-18-2013, 09:23 AM
|
#6
|
Senior Member
Join Date: Apr 2008
Location: Sunny San Diego
Posts: 2,214
|
Re: Is prevention of her2+ brain mets around the corner? Oral TKI Pazopanib
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?
__________________
Diagnosed 2007
Stage IIb Invasive Ductal Carcinoma, Pagets, 3 of 15 positive nodes
Traditional Treatment: Mastectomy and Axillary Node Dissection followed by Taxotere, 6 treatments and 1 year of Herceptin, no radiation
Former Chemo Ninja "Takizi Zukuchiri"
Additional treatments:
GP2 vaccine, San Antonio Med Ctr
Prescriptive Exercise for Cancer Patients
ENERGY Study, UCSD La Jolla
Reconstruction: TRAM flap, partial loss, Revision
The content of my posts are meant for informational purposes only. The medical information is intended for general information only and should not be used in any way to diagnose, treat, cure, or prevent disease
|
|
|
04-18-2013, 10:55 AM
|
#7
|
Senior Member
Join Date: Mar 2006
Posts: 4,778
|
Re: Is prevention of her2+ brain mets around the corner? Oral TKI Pazopanib
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.
|
|
|
04-18-2013, 11:43 AM
|
#8
|
Senior Member
Join Date: Feb 2012
Location: Ontario, Canada
Posts: 115
|
Re: Is prevention of her2+ brain mets around the corner? Oral TKI Pazopanib
Yes Alice, me too. Thanks Lani! Good news here!
__________________
[
Feb 2013 - NED
Mar 2013 - thought I had progression, watching brain.
April 2013 - GOT MARRIED!!!!
May 2013 - looks like no progression, but necrosis and bigger.
Oct-Dec 2013 - Avastin tx
Nov 2013 - MRI shows necrosis shrinkage!!!!
Jan 2014 - Lepto Mening. disease found
Feb 2014 - WBR
March - BLAHHHH
April 2014 - Liver mets found
April 2014 to present - Chemo again, whooohoo. Fun!
July 2014, scans look good.
Stay on Perjetand hercertin.
Nov. 2014 more lepto-mening disease more WBR.
Feb 2015 more lepto-mening disease in spine and neck. More radiation.
Start on TDM1 no more Perjeta stay on herceptin
March 2015 more radiation in my thoracic area, more lepto-meningial disease
April 2015 trying to walk again.
[/SIZE][/FONT]
|
|
|
Posting Rules
|
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts
HTML code is Off
|
|
|
All times are GMT -7. The time now is 03:29 PM.
|