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01-18-2011, 09:29 AM
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#1
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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drugs already approved indirectly attack breast cancer stem cells (responsible for bc
growth and spread).
I heard much about this at last year's AACR annual conference in Washington, DC in APril
Now it has been published(and via open access):
U-M researchers find indirect path to attack breast cancer stem cells
[University of Michigan Health System]
ANN ARBOR, Mich. — Scientists at the University of Michigan Comprehensive Cancer Center have identified a potential new way of attacking breast cancer stem cells, the small number of cells in a tumor that fuel its growth and spread. Researchers found that breast cancer stem cells are regulated by a type of cell derived from bone marrow, called mesenchymal stem cells. These cells are drawn from the bone marrow to the cancer and create a "niche" for the cancer stem cells, allowing them to replicate.
"The importance of this is that we may be able to attack breast cancer stem cells indirectly by blocking these signals from the niche," says study author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the University of Michigan Comprehensive Cancer Center.
Breast cancer stem cells were first identified by Wicha and colleagues at the University of Michigan in 2003. Cancer stem cells are believed to be resistant to current chemotherapies and radiation treatment, which researchers say may be the reason cancer so often returns after treatment.
Little is known about the cancer stem cell niche - a type of microenvironment that is highly associated with tumor growth and metastasis. The researchers looked at mesenchymal stem cells, which arise in bone marrow. They found that breast cancers in mice sent out signals which attracted mesenchymal stem cells from the bone marrow into the tumor where these cells interacted and stimulated the growth of breast cancer stem cells.
Researchers then identified two signals from a cytokine network - a type of protein that affects how cells communicate - that were responsible for stem cell regulation. These same cytokines play a role in inflammation and drugs that block them have already been approved for the treatment of inflammatory diseases such as rheumatoid arthritis. By blocking these cytokine signals, researchers hope that they can successfully target the cancer stem cell population providing a more effective treatment for breast cancer.
Results: of the study appear in the Jan. 15 issue of Cancer Research.
Additional authors: From U-M: Suling Liu, Sing J. Ou, Shawn Clouthier, Shivani H. Patel, Hasan Korkaya, Amber Heath, Julie Dutcher, Celina G. Kleer, Younghun Jung, Gabriela Dontu, Russell Taichman; from Centre de Recherche en Cancerologie de Marseille: Christophe Ginestier
Funding: National Institutes of Health, Taubman Research Institute
Disclosure: Wicha has financial holdings in OncoMed Pharmaceuticals, which has applied for a patent on cancer stem cell technologies.
OPEN ACCESS: Breast Cancer Stem Cells Are Regulated by Mesenchymal Stem Cells through Cytokine Networks
[Cancer Research]
We have used in vitro and mouse xenograft models to examine the interaction between breast cancer stem cells (CSC) and bone marrow-derived mesenchymal stem cells (MSC). We show that both of these cell populations are organized in a cellular hierarchy in which primitive aldehyde dehydrogenase expressing mesenchymal cells regulate breast CSCs through cytokine loops involving IL6 and CXCL7. In NOD/SCID mice, labeled MSCs introduced into the tibia traffic to sites of growing breast tumor xenografts where they accelerated tumor growth by increasing the breast CSC population. With immunochemistry, we identified MSC-CSC niches in these tumor xenografts as well as in frozen sections from primary human breast cancers. Bone marrow-derived MSCs may accelerate human breast tumor growth by generating cytokine networks that regulate the CSC population.
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01-20-2011, 07:08 AM
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#2
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Senior Member
Join Date: Feb 2008
Location: South East Wisconsin
Posts: 3,431
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Re: drugs already approved indirectly attack breast cancer stem cells (responsible fo
Quote:
Researchers then identified two signals from a cytokine network - a type of protein that affects how cells communicate - that were responsible for stem cell regulation. These same cytokines play a role in inflammation and drugs that block them have already been approved for the treatment of inflammatory diseases such as rheumatoid arthritis.
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Ok...which drugs?
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01-20-2011, 08:43 AM
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#3
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Senior Member
Join Date: Feb 2009
Posts: 1,526
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Re: drugs already approved indirectly attack breast cancer stem cells (responsible fo
I was wondering to!
Any idea Lani?
Thanks
Ellie
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01-20-2011, 03:44 PM
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#4
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Senior Member
Join Date: May 2010
Location: Melbourne, Australia
Posts: 434
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Re: drugs already approved indirectly attack breast cancer stem cells (responsible fo
I'd love to know too. I think I could develop rheumatoid arthritis.... Thanks Trish
__________________
5/2004 (R) 30mm bre gr3 infiltrating ductal ca 16/18nodes er (2+) pr (3+) HER2 (3+)
6/2004 6 cycles(FEC), Oct 40 rads, Tamoxifen
5/2006 oopherectomy, Arimedex
12/2006 liver mets largest 9cm
1/2007 Herceptin,
3/2007 Taxol + Herc
1/2008 Herc alone
4/2008 Multiple bone mets,Zometa
7/2008 Herc + Gemcitabine
8/2008 Herc+Navelbine/vinoralbine
10/2008 Herc+Carboplatin+Taxol
12/2008 Tykerb+Xeloda
2/2010 Herceptin + trial drug
5/2010 Herceptin+Tykerb
8/2010 Tykerb+Abraxane
9/2010 Abraxane
12/2010 Abraxane+Tyk+Herc
4/2011 Tyk+Herc+Femara
6/2011 Liver and bone mets prog.Abraxane continue Herceptin,Tykerb,Femara and Zometa
8/2011 Probable liver progression and increased neuropathy. Xeloda with Tyk+Herc. Zometa 6 weekly.
9/2011 Liver progression,TM +++. Cyclophosphamide and Methotrexate metro Herc Zometa
10/2011 liver mets prog.Herc, 3 Tykerb +2mg decodron daily,Zometa
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01-20-2011, 04:39 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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Re: drugs already approved indirectly attack breast cancer stem cells (responsible fo
I would love to know which drugs also?
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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01-24-2011, 12:18 AM
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#6
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Senior Member
Join Date: Feb 2008
Location: South East Wisconsin
Posts: 3,431
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Re: drugs already approved indirectly attack breast cancer stem cells (responsible fo
And so...
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01-24-2011, 04:57 AM
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#7
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Senior Member
Join Date: Jan 2008
Location: "Love never fails."
Posts: 5,809
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Re: drugs already approved indirectly attack breast cancer stem cells (responsible fo
__________________
Jackie07
http://www.kevinmd.com/blog/2011/06/doctors-letter-patient-newly-diagnosed-cancer.html
http://www.asco.org/ASCOv2/MultiMedi...=114&trackID=2
NICU 4.4 LB
Erythema Nodosum 85
Life-long Central Neurocytoma 4x5x6.5 cm 23 hrs 62090 semi-coma 10 d PT OT ST 30 d
3 Infertility tmts 99 > 3 u. fibroids > Pills
CN 3 GKRS 52301
IDC 1.2 cm Her2 +++ ER 5% R. Lmptmy SLNB+1 71703 6 FEC 33 R Tamoxifen
Recc IIB 2.5 cm Bi-L Mast 61407 2/9 nds PET
6 TCH Cellulitis - Lymphedema - compression sleeve & glove
H w x 4 MUGA 51 D, J 49 M
Diastasis recti
Tamoxifen B. scan
Irrtbl bowel 1'09
Colonoscopy 313
BRCA1 V1247I
hptc hemangioma
Vertigo
GI - > yogurt
hysterectomy/oophorectomy 011410
Exemestane 25 mg tab 102912 ~ 101016 stopped due to r. hip/l.thigh pain after long walk
DEXA 1/13
1-2016 lesions in liver largest 9mm & 1.3 cm onco. says not cancer.
3-11 Appendectomy - visually O.K., a lot of puss. Final path result - not cancer.
Start Vitamin D3 and Calcium supplement (600mg x2)
10-10 Stopped Exemestane due to r. hip/l.thigh pain OKed by Onco 11-08-2016
7-23-2018 9 mm groundglass nodule within the right lower lobe with indolent behavior. Due to possible adenocarcinoma, Recommend annual surveilence.
7-10-2019 CT to check lung nodule.
1-10-2020 8mm stable nodule on R Lung, two 6mm new ones on L Lung, a possible lymph node involvement in inter fissule.
"I WANT TO BE AN OUTRAGEOUS OLD WOMAN WHO NEVER GETS CALLED AN OLD LADY. I WANT TO GET SHARP EDGED & EARTH COLORED, TILL I FADE AWAY FROM PURE JOY." Irene from Tampa
Advocacy is a passion .. not a pastime - Joe
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01-24-2011, 05:04 AM
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#8
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Senior Member
Join Date: Feb 2009
Posts: 1,526
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Re: drugs already approved indirectly attack breast cancer stem cells (responsible fo
Thanks Jackie.
Makes you wonder,I have known a great many ppl on these types of drugs who never seem to develop cancer.
Ellie
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01-24-2011, 07:54 AM
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#9
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Senior Member
Join Date: Oct 2007
Posts: 1,851
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Re: drugs already approved indirectly attack breast cancer stem cells (responsible fo
Perhaps Rituxan (rituximab) is one such drug. This drug is used for certain types of non-Hodgkin's lymphoma, but also I believe for rheumatoid arthritis and is also an anti-inflammatory. I understand that cancer involves inflammation of a sort.
And Rich, you're right. Shoddy reporting.
Joan
__________________
Diagnosed stage 2b in July 2003 (2.3 cm, HER2+, ER-/PR-, 7+ nodes). Treated with mastectomy (with immediate DIEP flap reconstruction), AC + T/Herceptin (off label). Cancer advanced to lung in Jan. 2007 (1 cm nodule). Started Herceptin every 3 weeks. Lung wedge resection April 2007. Cancer recurred in lung April 2008. RFA of lung in August 2008. 2nd annual brain MRI in Oct. 2008 discovered 2.6 cm cystic tumor in left frontal lobe. Craniotomy Oct. 2008 (ER-/PR-/HER2-) followed by targeted radiation (IMRT). Coughing up blood Feb. 2009. Thoractomy July 2009 to cut out fungal ball of common soil fungus (aspergillus) that grew in the RFA cavity (most likely inhaled while gardening). No cancer, only fungus. Removal of tiny melanoma from upper left arm, plus sentinel lymph node biopsy in Feb. 2016. Guardant Health liquid biopsy in Feb. 2016 showed mutations in 4 subtypes of TP53. Repeat of Guardant Health biopsy in Jana. 2021 showed 3 TP53 mutations, BRCA1 mutation and CHEK2 mutation. Invitae genetic testing showed negative for all of these. Living with MBC since 2007. Stopped Herceptin Hylecta (injection) treatment in March 2020. Recent 2023 annual CT of chest, abdomen and pelvis and annual brain MRI showed NED. Praying for NED forever!!
Last edited by Joan M; 01-24-2011 at 07:56 AM..
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02-04-2011, 08:54 PM
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#10
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Guest
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Re: drugs already approved indirectly attack breast cancer stem cells (responsible fo
http://www.cancer.med.umich.edu/news...atment10.shtml
Repertaxin blocks interleukin 8 and interrupts a critical signal that allows breast cancers cells to grow. This may not be one of the drugs mentioned in the article you folks are discussing. But perhaps still useful information, so I wanted to make it available to you.
I'm not a cancer patient or a cancer survivor. I do in depth research related to investing in biotech and have a science background. I just happened onto your website while investigating the relationship between cancer stem cells and pro-inflammatory cell signalling.
Another already approved drug worth looking at is itraconazole. It's an anti-fungal that has been found to block the SHH pathway, which appears to play a role in cancer stem cell growth.
http://www.reyalab.org/manage/user_f...1274278169.pdf
Best to all.
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02-05-2011, 03:19 AM
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#11
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Senior Member
Join Date: May 2010
Location: Melbourne, Australia
Posts: 434
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Re: drugs already approved indirectly attack breast cancer stem cells (responsible fo
Thanks everyone.
Trish
__________________
5/2004 (R) 30mm bre gr3 infiltrating ductal ca 16/18nodes er (2+) pr (3+) HER2 (3+)
6/2004 6 cycles(FEC), Oct 40 rads, Tamoxifen
5/2006 oopherectomy, Arimedex
12/2006 liver mets largest 9cm
1/2007 Herceptin,
3/2007 Taxol + Herc
1/2008 Herc alone
4/2008 Multiple bone mets,Zometa
7/2008 Herc + Gemcitabine
8/2008 Herc+Navelbine/vinoralbine
10/2008 Herc+Carboplatin+Taxol
12/2008 Tykerb+Xeloda
2/2010 Herceptin + trial drug
5/2010 Herceptin+Tykerb
8/2010 Tykerb+Abraxane
9/2010 Abraxane
12/2010 Abraxane+Tyk+Herc
4/2011 Tyk+Herc+Femara
6/2011 Liver and bone mets prog.Abraxane continue Herceptin,Tykerb,Femara and Zometa
8/2011 Probable liver progression and increased neuropathy. Xeloda with Tyk+Herc. Zometa 6 weekly.
9/2011 Liver progression,TM +++. Cyclophosphamide and Methotrexate metro Herc Zometa
10/2011 liver mets prog.Herc, 3 Tykerb +2mg decodron daily,Zometa
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02-05-2011, 04:44 AM
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#12
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Senior Member
Join Date: Feb 2009
Posts: 1,526
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Re: drugs already approved indirectly attack breast cancer stem cells (responsible fo
Thanks to all and to unregistered for your interest. It's often good to have different perspectives.
Ellie
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02-05-2011, 07:26 AM
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#13
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Senior Member
Join Date: Jul 2010
Posts: 28
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Re: drugs already approved indirectly attack breast cancer stem cells (responsible fo
Do you think this is related to the reported decreased risk of recurrence associated with NSAIDs use?
http://www.ncbi.nlm.nih.gov/pubmed/17404892
__________________
IDC 6/2010
ER+PR+HER2+
Lumpectomy & SNB
0/2 nodes
2.7cm
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02-06-2011, 06:16 AM
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#14
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Senior Member
Join Date: Jan 2010
Location: Matakana which is one hour north of Auckland, New Zealand.
Posts: 89
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Re: drugs already approved indirectly attack breast cancer stem cells (responsible fo
What about dexamethasone (Decadron) as this used for rheumatoid arthritis and reduces inflammation.
__________________
Oct 2009 Masectomy 6 cm Tumor . Sentinal node biopsy , Node Positive . Her2 + er/pr -.
Nov 2009 X3 Taxane and Herceptin, X3 FEC
March 2010 25 Rads
March 2010 continued on Herception untill 16 Dec 2010
May 2010 Ultra Sound .... ALL CLEAR... NED
August 2010 started vaccine trial University of Washington
7th Dec 2010 finished vaccine trial
20th Dec 2010 Port removed
3rd Feb no longer ned brain mets
23r Feb start VMAT radiation
August 2011 two new mets to brain and others starting to grow again !!!!
August start tykerb and xeloda
Dec 1 MRI all small brain mets gone. Largest shrunk by 50% only three small ones to go 17mm,8mm,6mm. Mets on there way out. Yeah
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02-06-2011, 10:36 AM
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#15
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Senior Member
Join Date: Feb 2008
Location: South East Wisconsin
Posts: 3,431
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Re: drugs already approved indirectly attack breast cancer stem cells (responsible fo
Ah..I remember the Repertaxin/Il-8 article by Wicha. Searching on it today, now called Reparaxin, but still investigational:
http://www.biocentury.com/products/reparixin
Hadn't heard of the Itraconazol. But yes..it's available!
Joan, did you have some for the fungal ball? Seems like one might be able to justify some based on relatively common nail fungi:
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000916
Not sure which form (pill, solution) would be best for off label cancer use.
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02-06-2011, 11:29 AM
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#16
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Senior Member
Join Date: Sep 2005
Location: Alaska
Posts: 2,018
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Re: drugs already approved indirectly attack breast cancer stem cells (responsible fo
As long as we are speculating... (DebbieL, where are you?)
I have long wondered whether the supposedly beneficial effects of chemotherapy had more to do with the support drugs given during chemotherapy than they did with the chemotherapy, since trials do not separate those effects out. Is the torture of chemotherapy getting the "credit" for beneficial effects that are in reality provided by other drugs? Is the chemo essential, or not?
Is it the anti-inflammatory effects of steroids (that are given in order for the body to better tolerate such toxic therapy) the real workhorses that provide the initial magic of nonrecurrence, for example? And at the same time, do they start a chain of events that encourage recurrence farther down the road, such as from slower metabolism and greater weight gain? And how dependent are they on one's stage of development for their results -- favorable or unfavorable?
Maybe if endocrinologists were more involved in the understanding and application of our treatment we would have a more disciplined scientific approach to it.
AlaskaAngel
__________________
Dx 2002 age 51
bc for granny, aunt, cousin, sister, mother.
ER+/PR+/HER2+++, grade 3
IDC 1.9 cm, some DCIS, Stage 1, Grade 3
Lumpectomy, CAFx6 (no blood boosters), IMRT rads, 1 3/4 yr tamoxifen
Rads necrosis
BRCA 1 & 2 negative
Trials: Early detection OVCA; 2004 low-dose testosterone for bc survivors
Diet: Primarily vegetarian organic; metformin (no diabetes), vitamin D3
Exercise: 7 days a week, 1 hr/day
No trastuzumab, no taxane, no AI
NED
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02-06-2011, 05:39 PM
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#17
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Senior Member
Join Date: Oct 2007
Posts: 1,851
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Re: drugs already approved indirectly attack breast cancer stem cells (responsible fo
Rich,
Yes, I did. When I had the fungal ball, or mycetoma, in my lung, I took voriconazole, which is an advanced form of itraconazozle. I then came across an article last spring about itraconazole's potential use in blocking the Hedgehog pathway in cancer. I sent an e-mail to the scientist doing the research, asking whether voriconazole would have the same effect. Here's his answer (which I really appreciated, as he took the time to explain it):
Please be aware that I am not clinically trained and cannot advise you on your medical condition.
In response to your question, our article described an effect of itraconazole on the Hedgehog signaling pathway, which plays an important role in organizing the normal pattern of embryonic growth and development, and also can play a role in the abnormal growth of certain tumors.
The effect of itraconazole on Hedgehog signaling is by a mechanism distinct from its effect on fungal growth. Other antifungal drugs, including voraconazole (Vfend) act on fungal growth by a mechanism similar to that of itraconazole but, unlike itraconazole, do not efficiently inhibit the Hh pathway. We specifically tested several other azole antifungals (the class of drug that includes itraconazole and voraconazole) and saw little effect if any on Hedgehog signaling (voraconazole was completely inactive in affecting the Hedgehog pathway).
To help you think about this, imagine two keys that have similar shafts and can both open the same lock, but have very different bows (the part you hold when you are turning the key). In this analogy, the effect of itraconazole on the Hh pathway is due to the structure of the bow. Voraconazole is also able to inhibit fungal growth because it has a similar shaft, but not the Hedgehog pathway because the bow is very different.
I would therefore not expect your treatment with Vfend to have had much or any effect on the Hedgehog pathway. A separate question is what role the Hedgehog signaling pathway may have in breast cancer. I cannot answer that question, although we are interested and have attempted to obtain funding to study it (with no success thus far).
I hope this helps. I wish you all the best.
*****
I was hoping to get a lucky break since I took Vfend for four months. Genetech is also studying the Hedgehog pathway in breast cancer.
Joan
__________________
Diagnosed stage 2b in July 2003 (2.3 cm, HER2+, ER-/PR-, 7+ nodes). Treated with mastectomy (with immediate DIEP flap reconstruction), AC + T/Herceptin (off label). Cancer advanced to lung in Jan. 2007 (1 cm nodule). Started Herceptin every 3 weeks. Lung wedge resection April 2007. Cancer recurred in lung April 2008. RFA of lung in August 2008. 2nd annual brain MRI in Oct. 2008 discovered 2.6 cm cystic tumor in left frontal lobe. Craniotomy Oct. 2008 (ER-/PR-/HER2-) followed by targeted radiation (IMRT). Coughing up blood Feb. 2009. Thoractomy July 2009 to cut out fungal ball of common soil fungus (aspergillus) that grew in the RFA cavity (most likely inhaled while gardening). No cancer, only fungus. Removal of tiny melanoma from upper left arm, plus sentinel lymph node biopsy in Feb. 2016. Guardant Health liquid biopsy in Feb. 2016 showed mutations in 4 subtypes of TP53. Repeat of Guardant Health biopsy in Jana. 2021 showed 3 TP53 mutations, BRCA1 mutation and CHEK2 mutation. Invitae genetic testing showed negative for all of these. Living with MBC since 2007. Stopped Herceptin Hylecta (injection) treatment in March 2020. Recent 2023 annual CT of chest, abdomen and pelvis and annual brain MRI showed NED. Praying for NED forever!!
Last edited by Joan M; 02-06-2011 at 05:43 PM..
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