There are also Phase II clinical trails in breast cancer and non small cell lun

SYK signaling functions are mediated in concert with SRC family kinases, This subject is not fully under stood and, in particular it is not clear to what extent var ious SRC family kinases are interchangeable in this role within a given 17-AAG ic50 cell type. It is perhaps not coincidental that a SRC family kinase, FYN, was identified in the blue mod ule by WGCNA and that a strong co expression correla tion was found in SCLC TMAs and cell lines, Byers. et. al also reported activation of SRC family kinases in SCLC assessed via reverse phase protein arrays, On the other hand, FYN kinase inhibition had no effect on SCLC cell line survival, Clarifying the SYK FYN signaling connection in SCLC, and the possible redundancy of SRC family kinases may open avenues to productively deploy inhibi tory combination of SYK and FYN targeted therapy.<br><br> In the TMA patient dataset, we detected 2 groups of SCLC based on SYK FYN expression alone, Admittedly, this dataset is too small to reach conclusions, highlighting the need for larger Adriamycin 25316-40-9 patient populations. Nonetheless, our observations raise the pos sibility of distinct treatment strategies in SYK positive SCLC tumors, by analogy to lung tumors overexpressing EGFR, or HER2 breast cancers, whose response to tar geted therapy dramatically improves the outcome, Here we have implemented an alternative strategy to large scale sequencing, based on a systems view of signaling networks provided by gene co expression analysis. We respectfully submit that this approach can provide useful translational insights in the biology of specific cancer types.<br><br> Conclusions We have identified a robust co expression network based signature for SCLC tumors on three independent platforms, This signature was also conserved in SCLC cell lines. Within this SSHN network, we found twenty targe table kinases that were overexpressed in most, if not all of these platforms. Two tyrosine ABT-199 kinases SYK and FYN were overexpressed significantly in SCLC patients and cell lines by several independent bioinformatics and experimental methods, and distinguished between two potential groups of patients SYK FYN positive and negative. The SYK FYN positive SCLC cell lines exhib ited significant loss of viability and increased cell death in response to SYK siRNA, providing evidence for SYK as a novel oncogenic driver for SCLC. All SCLC patients get treated with combination chemotherapy without distinction.<br><br> Our work suggests that stratify ing patients with respect to SYK FYN expression may open avenues to personalized medicine in SCLC, given that SYK small molecule inhibitors are already in clinical trials for other disease conditions. Future work will have to determine whether in fact SYK may represent a poten tial actionable target in SCLC, by itself or in combination with chemo or radiation therapy. Stepwise progression of cancer malignancy has been clinically well defined, In the early stage, the cancer cells, confined to a very limited area, are not invasive and metastatic, whereas in the late stage, the cells, spreading to distant sites in the body, are highly invasive and metastatic.