beginnning of the end of her2+ breast cancer? Divide and conquer!

[Lani]

I have railed for years on the need to divide her2+ bc into subtypes in order to discover the best targets/ combination treatment for each subtype

I have also railed for years to encourage bone marrow sampling to discover if the disseminated tumor cells there could tell which patients needed systemic therapy as well as local treatment (surgery and/or radiation therapy) and to discover whether the initial therapy was successful or whether additional therapy against other targets is needed

I have not hidden that I believe in the cancer stem cell "theory" of breast cancer

Here scientists have found (in mice, but results corroborated when evaluating a cohort of human breast cancer patients accumulated by vantViver) that an 8 gene signature derived from cancer stem cells of her2+ breast cancer (in mice)
can stratify her2+ breast cancer patients prognoses and serve as targets for therapy.

Two of the genes can be affected by over the counter NSAIDs (cox1 and cox2) and an already FDA approved drug in use for many years -an iron chelator used for iron poisoning and inherited iron deposition diseases is available as well.

I am hopeful studies in this direction will help stratify her2+ breast cancer into groups (even though every patients tumor is unique) which can be treated similarly ie similar targets, turning her2+ breast cancer into an annoying chronic disease or even curing it.

I hope this approach can be used against other forms of cancer as well

Proteomics. 2012 Sep 19. doi: 10.1002/pmic.201200103. [Epub ahead of print]
Proteomic profiling of cancer stem cells derived from primary tumors of HER2/Neu transgenic mice.
Kanojia D, Zhou W, Zhang J, Jie C, Lo PK, Wang Q, Chen H.
Source
Department of Biological Science, Centre for colon cancer, University of South Carolina, Columbia, SC 29208, USA.
Abstract
HER2 overexpression leads to mammary tumorigenesis and its elevated levels leads to increase in cancer stem cells (CSCs), invasion and metastasis. CSCs are resistant to radiation/chemotherapeutic drugs and are believed to be responsible for recurrence/relapse of cancer. CSCs are isolated using flow cytometry based sorting, although reliable, this technology hinders the convenient identification of molecular targets of CSCs. Therefore to understand the molecular players of increased CSC through HER2 overexpression and to develop meaningful targets for combination therapy, we isolated and characterized breast CSCs through convenient tumorsphere culture. We identified the altered protein expression in CSC as compared to non-CSC using LC-MS/MS and confirmed those results using qRT-PCR and western blotting. Ferittin Heavy Chain 1 was identified as a candidate gene which is involved in iron metabolism and iron depletion significantly decreased the self-renewal of CSCs. We further performed in silico analysis of altered genes in tumorsphere and identified a set of genes (PTMA, S100A4, S100A6, TNXRD1, COX-1, COX-2, KRT14 and FTH1), representing possible molecular targets, which in combination showed a promise to be used as prognostic markers for breast cancer.
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PMID: 22997041

[Becky]

Lani

Does this mean that aspirin and Cox2 inhibitors (such as curcumin which is a natural Cox 2 inhibitor) may help those affected by the Cox pathway IF it is one of their devils?

Is this why aspirin can help?

Becky

[Lani]

aspirin is a cox1 and cox 2 inhibitor--but in order to get antiinflammatory blood levels you need to take several every 4 hours or so--as are ibuprofen, naproxen, sulindac and several others. Of the NSAIDs naproxen is felt to be the safest with respect to cardiovascular side effects--all can cause stomach bleeding and rarely kidney problems as well.

Celebrex is ONLY a cox 2 inhibitor. It is unclear what the anticancer dosage would be and how often it must be taken vs the antiinflammatory dosage and frequency.

It is just lovely that there are already approved drugs in these categories with well understood side effects/safety profiles.

[Ellie F]

Thanks Lani
Again more research towards a cure or long term management strategy.As you say it's really good that some drugs are already available.
Ellie

[Melissa]

Maybe all the ibuprofin I take for the aches from arimidix actually helps me! ha Not really funny but it is interesting.

[KristinSchwick]

I agree with Melissa- now I shouldn't hesitate when I need to reach for the Ibuprofen. Those joint aches are buzz killers.

[Rolepaul]

And these all cross the blood brain barrier! That is very interesting as Nina found relief and less disease in MRIs when she was on Celebrex with steroids. I think I will see if they will let her go back on. Naproxen and the others do not give the pain relief of Celebrex.

[KDR]

Thanks, Paul. And there is Dr. Zhang again...
Karen

[R.B.]

Please see last page of Omega 3 6 thread thanks Lani fascinating and not unexpected

http://her2support.org/vbulletin/sho...=24410&page=20


http://her2support.org/vbulletin/showthread.php?t=24410