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04-10-2007, 09:04 AM
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#1
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Senior Member
Join Date: Mar 2006
Posts: 4,783
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hot off the press--gene which causes her2+ breast cancer to metastasize found-target!
Jefferson scientists identify protein key to breast cancer spread, potential new drug target [Eureka News Service]
(PHILADELPHIA) Researchers at the Kimmel Cancer Center at Jefferson have identified a protein that they say is key to helping a quarter of all breast cancers spread. The finding, reported online the week of April 9, 2007 in the journal Proceedings of the National Academy of Sciences, could be a potential target for new drugs aimed at stopping or slowing the growth and progression of breast cancer.
Kimmel Cancer Center director Richard Pestell, M.D., Ph.D., professor and chair of cancer biology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and colleagues genetically engineered mice to lack the protein Akt1, which normally plays a role in keeping cells alive by interfering with programmed cell death. Breast and other cancers make an overabundance of the protein, and it's thought to potentially affect survival of breast and other cancer cells as well.
To test that hypothesis, Dr. Pestell and his team bred the mice missing the gene for Akt1 with other mice that overexpressed the HER2-neu (ErbB2) oncogene, which leads to approximately 25 percent of all breast cancers. They then examined the role of Akt in the onset and progression of breast cancer in the resulting offspring.
To their surprise, mice lacking two copies of the gene that produces Akt1 rarely had any tumors. Those mice that carried only one copy of the Akt1 gene developed some tumors, but they were small and developed more slowly. Mice with two copies of Akt1 rapidly developed significant cancer.
"The finding was exciting because it told us that Akt1 is a potentially useful target for ErbB2-positive breast cancer," Dr. Pestell says. "More interesting was that even if the mouse developed a tumor, it didn't develop metastases. We proved that there was a requirement for Akt1 in metastasis, which makes Akt1 an exciting target for metastatic breast cancer. We knew that Akt1 could play a role in cell growth and size, but the idea that it could play a role in migration and metastasis was an unexpected new finding,"
The researchers also proved how, showing that Akt1 causes the cancer cells to secrete a factor - CXCL16 - that promotes breast cancer cell migration. Without Akt, cancer cells failed to migrate. They also showed that deleting Akt1 completely blocked breast cancer metastasis to the lungs, while mice that expressed Akt1 died from lung metastasis.
While scientists have looked at Akt as a drug target, notes Arthur Pardee, Ph.D., professor emeritus of medical oncology at the Dana-Farber Cancer Institute in Boston, its role in metastasis is less emphasized. "Blocking this with anti-Akt drugs might provide a novel treatment, especially against early cancers," he says.
While the monoclonal antibody drug Herceptin has been very successful in treating ErbB2-positive breast cancer, patients can relapse, Dr. Pestell notes, and other drug targets are needed. The newly found secreted factor may prove to be such a target.
"We'd like to find a way of blocking CXCL16 production and see if it's true in human breast cancers," Dr. Pestell says. "Right now we are looking at patients' samples to see whether this is important in promoting metastatic breast cancer of other types."
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04-10-2007, 09:13 AM
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#2
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Senior Member
Join Date: Oct 2005
Location: New Jersey
Posts: 3,154
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Great News!
Now lets pray they can get to the next time step quickly! We need this yesterday.
Jean
__________________
Stage 1, Grade 1, 3/30/05
Lumpectomy 4/15/05 - 6MM IDC
Node Neg. (Sentinel node)
ER+ 90% / PR-, Her2+++ by FISH
Ki-67 40%
Arimidex 5/05
Radiation 32 trt, 5/30/05
Oncotype DX test 4/17/06, 31% high risk
TOPO 11 neg. 4/06
Stopped Arimidex 5/06
TCH 5/06, 6 treatments
Herceptin 5/06 - for 1 yr.
9/06 Completed chemo
Started Femara Sept. 2006
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04-10-2007, 01:18 PM
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#3
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Senior Member
Join Date: Nov 2005
Posts: 943
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Interesting stuff. If its true, maybe there is a genetic basis for her2.
__________________
Robin
2002- dx her2 positive DCIS/bc TX Mast, herceptin chemo
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04-10-2007, 01:31 PM
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#4
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Senior Member
Join Date: Oct 2005
Posts: 3,519
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Hurry, hurry, hurry Dr. Pestell!!! This is wonderful news...
__________________
Brenda
NOV 2012 - 9 yr anniversary
JULY 2012 - 7 yr anniversary stage IV (of 50...)
Nov'03~ dX stage 2B
Dec'03~ Rt side mastectomy, Her2+, ER/PR+, 10 nodes out, one node positive
Jan'04~ Taxotere/Adria/Cytoxan x 6, NED, no Rads, Tamox. 1 year, Arimadex 3 mo., NED 14 mo.
Sept'05~ micro mets lungs/chest nodes/underarm node, Switched to Aromasin, T/C/H x 7, NED 6 months - Herceptin only
Aug'06~ micro mets chest nodes, & bone spot @ C3 neck, Added Taxol to Herceptin
Feb'07~ Genetic testing, BRCA 1&2 neg
Apr'07~ MRI - two 9mm brain mets & 5 punctates, new left chest met, & small increase of bone spot C3 neck, Stopped Aromasin
May'07~ Started Tykerb/Xeloda, no WBR for now
June'07~ MRI - stable brain mets, no new mets, 9mm spots less enhanced, CA15.3 down 45.5 to 9.3 in 10 wks, Ty/Xel working magic!
Aug'07~ MRI - brain mets shrunk half, NO NEW BRAIN METS!!, TMs stable @ 9.2
Oct'07~ PET/CT & MRI show NED
Apr'08~ scans still show NED in the head, small bone spot on right iliac crest (rear pelvic bone)
Sept'08~ MRI shows activity in brain mets, completed 5 fractions/5 consecutive days of IMRT to zap the pesky buggers
Oct'08~ dropped Xeloda, switched to tri-weekly Herceptin in combo with Tykerb, extend to tri-monthly Zometa infusion
Dec'08~ Brain MRI- 4 spots reduced to punctate size, large spot shrunk by 3mm, CT of torso clear/pelvis spot stable
June'09~ new 3-4mm left cerrebellar spot zapped with IMRT targeted rads
Sept'09~ new 6mm & 1 cm spots in pituitary/optic chiasm area. Rx= 25 days of 3D conformal fractionated targeted IMRT to the tumors.
Oct'09~ 25 days of low dose 3D conformal fractionated targeted IMRT to the bone mets spot on rt. iliac crest that have been watching for 2 years. Added daily Aromasin back into treatment regimen.
Apr'10~ Brain MRI clear! But, see new small spot on adrenal gland. Change from Aromasin back to Tamoxifen.
June'10~ Tumor markers (CA15.3) dropped from 37 to 23 after one month on Tamoxifen. Continue to monitor adrenal gland spot. Remain on Tykerb/Herceptin/Tamoxifen.
Nov'10~ Radiate positive mediastinal node that was pressing on recurrent laryngeal nerve, causing paralyzed larynx and a funny voice.
Jan'11~ MRI shows possible activity or perhaps just scar tissue/necrotic increase on 3 previously treated brain spots and a pituitary spot. 5 days of IMRT on 4 spots.
Feb'11~ Enrolled in T-DM1 EAP in Denver, first treatment March 25, 2011.
Mar'11~ Finally started T-DM1 EAP in Denver at Rocky Mountain Cancer Center/Rose on Mar. 25... hallelujah.
"I would rather be anecdotally alive than statistically dead."
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04-10-2007, 01:34 PM
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#5
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Senior Member
Join Date: Feb 2006
Location: Southern, CA
Posts: 2,511
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Jean, You took the words right out of my mouth. Very encouraging.
Chelee
__________________
DX: 12-20-05 - Stage IIIA, Her2/Neu, 3+++,Er & Pr weakly positive, 5 of 16 pos nodes.
Rt. MRM on 1-3-06 -- No Rads due to compromised lungs.
Chemo started 2-7-06 -- TCH - - Finished 6-12-06
Finished yr of wkly herceptin 3-19-07
3-15-07 Lt side prophylactic simple mastectomy. -- Ooph 4-05-07
9-21-09 PET/CT "Recurrence" to Rt. axllia, Rt. femur, ilium. Possible Sacrum & liver? Now stage IV.
9-28-09 Loading dose of Herceptin & started Zometa
9-29-09 Power Port Placement
10-24-09 Mass 6.4 x 4.7 cm on Rt. femur head.
11-19-09 RT. Femur surgery - Rod placed
12-7-09 Navelbine added to Herceptin/Zometa.
3-23-10 Ten days of rads to RT femur. Completed.
4-05-10 Quit Navelbine--Herceptin/Zometa alone.
5-4-10 Appt. with Dr. Slamon to see what is next? Waiting on FISH results from femur biopsy.
Results to FISH was unsuccessful--this happens less then 2% of the time.
7-7-10 Recurrence to RT axilla again. Back to UCLA for options.
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04-10-2007, 08:21 PM
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#6
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Senior Member
Join Date: Jun 2006
Location: Bradenton,FL
Posts: 977
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Where can I donate my tissue, blood ...ANYTHING !!!! Id like to hurry this thing along as well!
Marcia
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04-12-2007, 05:42 AM
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#7
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Senior Member
Join Date: Jun 2006
Location: Bradenton,FL
Posts: 977
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Lani, I received an interesting abstract today from Nature/science re Her2 . If you like to see it let me know.
Warmly, Marcia
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04-12-2007, 09:33 PM
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#8
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Senior Member
Join Date: Mar 2006
Posts: 4,783
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always eager for additional information
My hard disc died almost two weeks ago and I have been using other computers, was limited to dial-up while out of town and have experienced other factors which have
challenged my information gathering (and storing) of late...
Just post it (or a link) here
Thanks!
Lani
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04-13-2007, 01:53 PM
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#9
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Junior Member
Join Date: Jan 2007
Location: North Carolina mountains
Posts: 1
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This is exciting news.....I am on board with "let's get this thing going"....I will donate any number of times (samples) to help with the progression.
<TABLE cellSpacing=2 cellPadding=0 border=0><TBODY><TR><TD>Biography:
Married, 53, two sons </TD></TR><TR><TD>Location:
North Carolina mountains </TD></TR><TR><TD>Interests:
gardening, reading, hiking, walking </TD></TR><TR><TD>Occupation:
dental office </TD></TR><TR><TD>Diagnosis and Treatment:
Diagnosed 8/31/06 with Stage 1, invasive ductal carcinoma; HER2 pos; 4 cancer cells in the sentinel node; 4 rounds of AC; 4 rounds of Taxol; 1 year of Herceptin; 33 treatments of radiation therapy. </TD></TR></TBODY></TABLE>
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04-13-2007, 05:14 PM
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#10
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Junior Member
Join Date: Jan 2007
Posts: 2
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I, too, would be more than willing to donate any samples needed. This sounds so very positive--the next step up from Herceptin.
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