Identifying and Targeting Mechanisms of Resistance to Braf Inhibitors, Paperb...
$ 22.83
Description
Identifying and Targeting Mechanisms of Resistance to Braf Inhibitors, Paperback by Babagana, Mahamat, ISBN 1976112761, ISBN-13 9781976112768, Brand New, Free shipping in the US Cutaneous melanoma is the most fatal type of skin cancer. The steady increase in incidence and static mortality rates have intensified the need to improve melanoma therapeutics. Constitutive activation of the growth signaling mitogen activated protein kinase (MAPK) pathway, frequently due to mutations in the proto-oncoprotein BRAF (BRAFV600E), has been found to provide the perpetual mitogenic signal needed for continued proliferation in many cancers, including melanoma. Although direct targeting of BRAF signaling has had some benefit for patients in the treatment of metastatic melanoma, it does not suffice in providing a lasting cure among the majority of responders due to acquired resistance. Additionally, a large subset of patients, who contain mutant BRAF, do not respond to BRAF inhibition due to intrinsic resistance. Because of the high occurrence of activating BRAF mutations in melanoma and other cancers and the limited efficacy of MAPK pathway targeting drugs due to acquired and intrinsic resistance, there is an immense need to identify additional strategies that can be used to safely increase the efficacy of MAPK pathway inhibitors. Here we demonstrate that the serine/threonine p21 activated kinase (PAK1) is a converging point used by several pathways to provide resistance to MAPK pathway inhibitors. Moreover, PAK1 inhibition can revert acquired and intrinsic resistance to MAPK pathway inhibitors. In addition, we show that polo-like kinase 3 (PLK3) can modulate MAPK pathway inhibitor efficacy in vitro and in vivo. Concurrently, there is a significant correlation of increased PLK3 expression in relapsed patient tumors and in many melanoma cell lines that are relatively resistant to MAPK pathway inhibitors. We have also identified that increased stimulation of the serine/threonine kinase, AKT, which itself has be shown to drive cancer progression and resistance to many types of therapy, including BRAF inhibitors, enhances cellular toxicity associated with exposure to increased temperatures. Our results identify patient subgroups who are at high risk for failure to current targeted therapeutics used for the treatment of BRAF mutated cancers. Additionally, we identify novel avenues which could be targeted to increase the efficacy of MAPK pathway inhibitors in melanoma and other BRAF mutated cancers. Our findings also support hyperthermia as a therapeutic approach which could be used to selectivity target a wide range of cancers cells with increased AKT signaling.
Book was in excellent new condition as described. Book arrived in great shape. Excellent overall cost. There was a shipping problem however, there were 3 books labeled as shipping together, but 2 separate packages were used and both had same tracking number so first package triggered delivered status on all 3 books even though only 2 arrived, the second package with book 3 came next day. So if you dont get one of your books when it says delivered you might wait a couple days for the 2nd package.
On the hunt for this particular cover art, the seller was very helpful with guidance on how to confirm through an ISBN search with the publisher. That solidified my choice to purchase from this seller. The book was packaged well for shipping and protection during travels. I'm extremely pleased with the pricing coupled with the mint condition of the book and the fast shipping (considering the hinderances caused by the current winter conditions). Great transaction and I will shop with them again!
As pictured / as described. Shipping - I ordered Dec 12 and glanced to see something like "Arrives ... 17th-21st", quickly thinking, "OK - plenty of time for Christmas". When it didn't show up, I went back to find it was actually "January 14th-17th" - oops! my goof! Wasn't expecting 5 week shipping. But ultimately, it did come in on Dec 26th, so quicker than the stated and might have been even quicker if not for holidays. Otherwise, good packing. Quick, easy transaction. Thanks!
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