By Richard M. Schultz (auth.), Prof. Dr. Paul L. Herrling, Alex Matter M.D., Dr. Richard M. Schultz (eds.)
There were large advances in our figuring out of molecular and tumor biology in the past few years. within the box of melanoma therapeutics, it's anticipated that cytotoxic drug techniques should be progressively changed with remedies in line with organic precise techniques. with a bit of luck those new certain cures will considerably bring up efficacy and absence the devastating and problematical unwanted effects elicited through cytotoxic chemotherapy.
This quantity is the 1st ebook to hide the overall subject of distinctive melanoma remedy. It offers a variety of pursuits corresponding to tumor angiogenesis, mobilephone cycle keep watch over and cellphone signalling, COX-2, apoptosis/cell survival, invasion and metastasis and methods like kinase inhibitors, antisense, and antibody-based therapeutics. The emphasis is on preclinical improvement, together with goal validation, improvement of biomarkers, innovations for mixture techniques, and improvement of resistance. the actual demanding situations all in favour of translating those facts to medical program are mentioned.
This quantity could be of huge basic curiosity to researchers and clinicians occupied with melanoma remedy in addition to different scientists attracted to present ideas for melanoma treatment.
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Extra info for Advances in Targeted Cancer Therapy
Moreover, emergence of resistance clones to single-agent therapy, whose main mechanism of action is directed against one specific target in a tumor, is likely to occur due to selection pressure, regardless of the drug’s molecular promiscuity. It has been hypothesized that combination of novel agents with cytotoxic chemotherapy will result in enhanced antitumor effects. Four phase III well-designed and adequately powered trials, with over 4000 NSCLC patients combined, comparing the combination of the EGFR tyrosine kinase inhibitors and standard chemotherapy to standard chemotherapy alone did not meet either the primary endpoint of survival or the secondary endpoints of time to disease progression or response rates, thus indicating that concomitant administration of these agents does not add clinical benefit to conventional chemotherapy in NSCLC [52–55].
Ideally, the targeted pharmacodynamic endpoint will have been shown to correlate with tumor response in animal models before its use for dose finding. However, primary drug targets are seldom known with certainty before phase I trials commence. For example, FT inhibitors were designed to inhibit the post-translational modification of ras, which they do, yet they exhibit activity against ras-independent tumors. Similarly, sorafenib was developed as a raf kinase inhibitor, but its antitumor activity in clinical testing seems more consistent with its activity as an inhibitor of VEGF receptor tyrosine kinase.
J Clin Oncol 19: 843–850 Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA et al ( 2004) Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-smallcell lung cancer. J Clin Oncol 22: 2184–2191 Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA (2003).