The full text of this article might say exactly what % of RCCs overexpress MAP kinase (likely upregulated by raf kinase):
>>Oncogene. 1999 Jan 21;18(3):813-22.
Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signaling pathway in human tumors.
Hoshino R, Chatani Y, Yamori T, Tsuruo T, Oka H, Yoshida O, Shimada Y, Ari-i S, Wada H, Fujimoto J, Kohno M.
Laboratory of Cell Regulation, School of Pharmaceutical Sciences, Nagasaki University, Japan.
The 41-kDa and 43-kDa mitogen-activated protein (MAP) kinases play a pivotal role in the mitogenic signal transduction pathway and are essential components of the MAP kinase cascade, which includes MAP kinase kinase (MEK) and Raf-1. As aberrant activation of signal transducing molecules such as Ras and Raf-1 has been linked with cancer, we examined whether constitutive activation of the 41-/43-kDa MAP kinases is associated with the neoplastic phenotype of 138 tumor cell lines and 102 primary tumors derived from various human organs. Constitutive activation of the MAP kinases was observed in 50 tumor cell lines (36.2%) in a rather tissue-specific manner: cell lines derived from pancreas, colon, lung, ovary and kidney showed especially high frequencies with a high degree of MAP kinase activation, while those derived from brain, esophagus, stomach, liver and of hematopoietic origin showed low frequencies with a limited degree of MAP kinase activation. We also detected constitutive activation of the 41-/43-kDa MAP kinases in a relatively large number of primary human tumors derived from kidney, colon and lung tissues but not from liver tissue. Many tumor cells, in which point mutations of ras genes were detected, showed constitutive activation of MAP kinases, however, there were also many exceptions to this observation. In contrast, the activation of the 41-/43-kDa MAP kinases was accompanied by the activation of Raf-1 in the majority of tumor cells and was completely associated with the activation of MEK and p90rsk in all the tumor cells examined. These results suggest that the constitutive activation of 41-/43-kDa MAP kinases in tumor cells is not due to the disorder of MAP kinases themselves, but is due to the disorder of Raf-1, Ras, or some other signaling molecules upstream of Ras.<<
PRs related to Bay 43-9006 mention that 90% of pancreatic cancers have this raf kinase upregulation issue, but doesn't assign a number to kidney cancers. I've had trouble finding anything specific how about how widely overexpressed raf kinase is in kidney cancer; Ill gladly accept help. Why results in colon cancer have been more disappointing is not clear to me; perhaps an alternate pathway for cell growth is available for those cell lines.
Some more color on the results and trial design:
eurekalert.org
pennhealth.com
The molecule hasn't seen a lot of discussion on the ONXX thread; maybe elsewhere such as in the Indications -- Cancer thread, but the SI search engine is challenged to find anything. The thread itself is not active or easy to find, so here's the link:
Subject 9228
Despite Miljenko's reservations, I'm not inclined to short this now, until I can find support for those reservations.
Cheers, Tuck |
