Avid Bioservices Inc (CDMO)

[Chocolate Moose]

I found this interesting from our associate Dr Weiss on nsclc and tki inhibitors. Sorry if its old news.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0030820


some snippets

While effective treatments for KRAS-driven tumors have generally been lacking, significant progress has been made in the development of tyrosine kinase inhibitors (TKI) that selectively block the activity of constitutively activated RTKs [4]. Perhaps the best example of this therapeutic strategy is the development of small-molecule inhibitors of EGFR, including gefitinib and erlotinib [5], [6]. Patients with specific activating mutations to EGFR respond favorably to these drugs, though most eventually relapse or progress due to a variety of acquired resistance mechanisms [7].

Interestingly, treatment of NSCLC cells with the JAK1/2 inhibitor ruxolitinib has no effect on cell proliferation and viability in two-dimensional culture, but inhibits growth in soft agar and xenograft assays. These data demonstrate that JAK2/STAT3 signaling operates independent of known driver mutations in NSCLC and plays critical roles in tumor cell behavior that may not be effectively inhibited by drugs that selectively target these driver mutations.

Our data demonstrate that STAT3 activity is unaffected by TKI treatment in several different cellular contexts.

Targeted Kinase Inhibitors Fail to Downregulate STAT3 Phosphorylation