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Researchers identify new, cancer-causing role for protein
By Dross at 2009-08-28 02:05

HOUSTON - The mainstay immune system protein TRAF6 plays an unexpected, key role activating a cell signaling molecule that in mutant form is associated with cancer growth, researchers at The University of Texas M. D. Anderson Cancer Center report in the Aug. 28 edition of Science.

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Molecular differences between early and advanced melanomas could provide new drug targets
By Dross at 2007-03-13 22:13

- Editors note. Akt is a target in a large number of metastaticterm cancers. 


The cell-signaling molecule Akt is a primary trigger that leads malignant melanomas on the skin's surface to begin growing vertically beneath the skin and turn into deadly invasive cancers, scientists have found. Understanding this key molecular difference between radial melanomas that spread on the surface of the skin and melanomas that grow vertically and invasively could provide new targets for the development of drugs to treat individuals with advanced stage melanomas.

Radial melanomas that have not spread below the skin can be treated surgically and have a survival rate of 98 percent beyond five years, according to the American Cancer Society. But when melanomas grow downward, the tumors become highly resistant to chemotherapyterm and radiation and the five-year survival rate falls rapidly, to 64 percent if the disease has reached the lymph nodes and 16 percent if it has spread to other organs.

read more | 1362 reads

'Bridge' protein spurs deadliest stages of breast cancer
By Dross at 2007-02-22 22:28

New role for protein yields promising lead for metastasistermterm prevention A protein known for its ability to "bridge" interactions between other cellular proteins may spur metastasis in breast cancer, the disease's deadliest stage, a study from Burnham Institute for Medical Research has found. Led by professor Gen-Sheng Feng, Ph.D., and colleagues at Burnham and Royal Victoria Hospital in Montreal, Quebec, the study ranks among the first to more precisely define the cancer role for the protein known as Gab-2. These results, to be published in the journal Oncogene, have been made available to the worldwide medical research community by priority posting online at the journal's website. The protein has been of keen research interest for its role in breast cancer, but whether it controlled metastasis or initial tumor growth was unknown. Gab-2 is one of a group of proteins known as "scaffold" or "bridge" proteins, which provide a molecular intermediary to help cell signal proteins interact.

read more | 1962 reads

First Dual inhibitor of AKT and S6K to Enter Clinical Development
By HCat at 2007-02-02 10:53

    The compound, XL418 is an inhibitor of protein kinase B (PKB or AKT) and S6 Kinase (S6K), key components of the phosphoinosotide-3 kinase (PI3K) signaling pathway. Activation of these kinases is a frequent event in human tumors, promoting cell growth, survival and resistance to chemotherapyterm and radiotherapy.


   "One of our drug development strategies is to systematically target key nodes in signaling pathways that are frequently deregulated in human tumors. An important component of this strategy is our focus on signaling downstream of PI3K," said Gisela Schwab, senior vice president at Exelixis.

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Downregulation of VEGF-A, STAT5 and AKT in acute myeloid leukemia blasts of patients treated with SU5416.
By admin at 2006-12-20 03:55

[via Entrez PubMed]:

Interesting article re a tyrosine kinase inhibitor Sugen is developing. I love to see real translational research, using patients' cells in trials and doing molecular assays for effects. In this case the researchers are demonstrating down regulation of VEGFterm messenger RNA levels, which is an assumption of down regulation in the final protein product.

In acute myeloid leukemiaterm (AML), autocrine or paracrine activation of receptor tyrosine kinases such as c-kit and FLT3 contributes to proliferation and apoptosis resistance of leukemic blasts. This provided the rationale for a multicenter clinical trial in patients with refractory AML with SU5416, a small molecule kinase inhibitor which blocks phosphorylation of c-kit, FLT3, VEGFR-1, VEGFR-2 (KDR) and VEGFR-3. The levels of VEGF mRNA expression were investigated in peripheral blood leukemic blasts taken from AML patients before and during treatment with SU5416. Rapid down regulation of VEGF was observed in AML blasts from 72% (13 of 18) of patients analysed. Patients initially expressing high VEGF-levels had a stronger downregulation and a higher clinical response rate (mean 865-fold, n = 10, P = 0,01) than patients initially expressing low VEGF-levels (mean four-fold, n = 8). These results suggest that abnormal high VEGF expression is downregulated by SU5416 treatment, and furthermore that decreases in VEGF mRNA levels may provide an early marker of therapeutic response with anti-angiogenic therapy. Additionally, protein expression of STAT5 and AKT was assessed by western blotting in these patient samples, as well as in the leukemia cell line, M-07e, treated in vitro with SU5416 as a model system. In the AML patient samples, parallel downregulation of both STAT5 and AKT was observed in several cases (STAT5 in four of 15; AKT in three of six examined patients). These effects were confirmed with the cell line M-07e after incubation with SU5416 in vitro using concentrations that are achievable in patients. In summary, our data show suppression of the expression of VEGF and key signal transduction intermediates in AML blasts during treatment with SU5416.

read more | 2590 reads

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