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Journal of the National Cancer Institute Advance Access originally published online on June 10, 2008
JNCI Journal of the National Cancer Institute 2008 100(12):833-835; doi:10.1093/jnci/djn189
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© The Author 2008. Published by Oxford University Press.

EDITORIALS

Resolving "Kinks" of Chemotherapy in Melanoma

Stergios J. Moschos, Preet M. Chaudhary, John M. Kirkwood

Affiliation of authors: Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA

Correspondence to: John M. Kirkwood, MD, Department of Medicine, University of Pittsburgh Cancer Institute, Hillman Cancer Center, Research Pavilion, Suite 1.32c, 5117 Centre Avenue, Pittsburgh, PA 15213-2584 (e-mail: kirkwoodjm@upmc.edu).

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A recent review of our last 35 years of phase 2 clinical trials for metastatic melanoma demonstrates that there has been no statistically significant improvement in 1-year overall survival or 6-month progression-free survival with any intervention tested in multicenter trials to date (1). An understanding of the basis of failure for these tested agents has generally been lacking, and few of these trials involved laboratory corollary studies of mechanism. Many cell survival and death pathways that are dysregulated in melanoma [reviewed in (2)] and other new pathways that might explain the refractoriness of melanoma to current treatments are under exploration (3). Melanoma repopulating (stem) cells that are resistant to chemotherapy may also be culpable (4). Targeting molecules critical for melanoma cell survival in rational combinations may improve the efficacy of chemotherapy, and this is currently being tested in relation to sorafenib.

Nuclear . . . [Full Text of this Article]


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