Replies to post #20696 on Ariad Pharmaceuticals Inc fka ARIA

[iandy]

The simple fact is that NVS has gleevec and tasigna in cml, ldk378 in alk, and affinitor in the mTor space.

I used to make this mistake all the time, still do sometimes.
I get some idea in my brain and then take every available piece of information that might buttress my idea and use it to make my case.
Unfortunately, I often don't know have enough knowledge on the subject at hand to understand I am wrong.
That's why I ask lots of questions.

IMO,NVS is not going to just roll over and buy Ariad rather than compete. One just has to look at the MS space to see many companies competing for the same patients. A couple of years ago I would have thought some of the long in the tooth MS drugs would have been extinct by now, but they are still widely prescrbed. The best drug isn't automatically the most profitable.
On the other hand, Biogen did buy 1/2 of Tysabri thinking it would dominate:)

If a play for Ariad is going to be made, I would expect it to come from another large player.

[ariadndndough]

http://clincancerres.aacrjournals.org/content/18/13/3592.abstract?sid=548faf8a-16f0-4075-8cf1-e62dfbc4c6a3

Paracrine Receptor Activation by Microenvironment Triggers Bypass Survival Signals and ALK Inhibitor Resistance in EML4-ALK Lung Cancer Cells
Tadaaki Yamada1, Shinji Takeuchi1, Junya Nakade1, Kenji Kita1, Takayuki Nakagawa1,2, Shigeki Nanjo1, Takahiro Nakamura3, Kunio Matsumoto3, Manabu Soda4, Hiroyuki Mano4, Toshimitsu Uenaka2, and Seiji Yano1
+ Author Affiliations

Authors' Affiliations: 1Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa; 2Tsukuba Research Laboratories, Eisai co., ltd., Ibaraki; 3Division of Tumor Dynamics and Regulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa; and 4Division of Functional Genomics, Jichi Medical University, Shimotsuke, Tochigi, Japan
Corresponding Author:
Seiji Yano, Division of Medical Oncology, Cancer Research Institute, Kanazawa University 13-1, Takara-machi, Kanazawa, Ishikawa 920-0934, Japan. Phone: [phone]; Fax: [phone]; E-mail: [e-mail]
Abstract
Purpose: Cancer cell microenvironments, including host cells, can critically affect cancer cell behaviors, including drug sensitivity. Although crizotinib, a dual tyrosine kinase inhibitor (TKI) of ALK and Met, shows dramatic effect against EML4-ALK lung cancer cells, these cells can acquire resistance to crizotinib by several mechanisms, including ALK amplification and gatekeeper mutation. We determined whether microenvironmental factors trigger ALK inhibitor resistance in EML4-ALK lung cancer cells.

Experimental Design: We tested the effects of ligands produced by endothelial cells and fibroblasts, and the cells themselves, on the susceptibility of EML4-ALK lung cancer cell lines to crizotinib and TAE684, a selective ALK inhibitor active against cells with ALK amplification and gatekeeper mutations, both in vitro and in vivo.

Results: EML4-ALK lung cancer cells were highly sensitive to ALK inhibitors. EGF receptor (EGFR) ligands, such as EGF, TGF-a, and HB-EGF, activated EGFR and triggered resistance to crizotinib and TAE684 by transducing bypass survival signaling through Erk1/2 and Akt. Hepatocyte growth factor (HGF) activated Met/Gab1 and triggered resistance to TAE684, but not crizotinib, which inhibits Met. Endothelial cells and fibroblasts, which produce the EGFR ligands and HGF, respectively, decreased the sensitivity of EML4-ALK lung cancer cells to crizotinib and TAE684, respectively. EGFR-TKIs resensitized these cells to crizotinib and Met-TKI to TAE684 even in the presence of EGFR ligands and HGF, respectively.

Conclusions: Paracrine receptor activation by ligands from the microenvironment may trigger resistance to ALK inhibitors in EML4-ALK lung cancer cells, suggesting that receptor ligands from microenvironment may be additional targets during treatment with ALK inhibitors. Clin Cancer Res; 18(13); 3592–602. ©2012 AACR.

This article is featured in Highlights of This Issue, p. 3493

Footnotes
Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).
Received November 21, 2011.
Revision received March 28, 2012.
Accepted April 17, 2012.
©2012 American Association for Cancer Research.
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[mejs]

Don, I think you would agree that ARIA will NOT remain Independent.Gleevec is going generic and NVS has stated that Oncology is a core and strategic business for them.As Harvey has stated ARIA is moving along to be a major player(company) in Oncology and imho NVS wants to protect and expand its position in Oncology.I think NVS will take an equity position with a Standstill Agreement as I have often stated.

In the final analysis it does not really matter who ARIA hooks up with as long as its a great deal.Don, Thanks for your information and insight.Again I am allowed only one post per day by IHub civic08801