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View the Table of Contents for the February 15 issue of Cancer Research.
Page 1415
Shields et al. Page 1502
The majority of human melanomas harbor activating mutations of either N-RAS or its downstream effector B-RAF, which cause activation of MEK and the ERK mitogen-activated protein kinase cascade. The melanoma-relevant effectors of ERK activation, however, are largely unknown. Shields et al. showed that increased ERK activation correlates strongly with mutational status of N-RAS or B-RAF in 21 melanoma cell lines. Melanoma lines that were wild-type for RAS/RAF showed low levels of ERK activation comparable to primary human melanocytes. Their results demonstrated a molecularly distinct melanoma subtype that does not require ERK activation or epithelial-mesenchymal transformation for progression.
Sawada et al. Page 1670
The hepatocyte growth factor receptor c-Met is a receptor tyrosine kinase that plays an important role in tumor growth and metastasis. Sawada et al. determined that c-Met is highly expressed in a subset of ovarian cancer patients and that it is an independent prognostic factor indicating an adverse prognosis. The authors provided mechanistic evidence that the inhibition of c-Met can reduce adhesion, invasion, tumor burden and, ultimately, metastasis by down-regulating the fibronectin receptor, a5β1-integrin, and the expression of proteases. These results defined a previously unrecognized role for c-Met in ovarian cancer adhesion and invasion and identified c-Met as an attractive treatment target in advanced ovarian cancer.
To further develop gene therapy for patients with glioblastomas, Jacobs et al. established an experimental gene therapy protocol comprising a series of imaging parameters including non-invasive assessment of viable tumor tissue (FLT-PET) followed by targeted application of HSV-1 amplicon vectors and quantification of “tissue-dose” of vector-mediated gene expression (FHBG-PET) and induced therapeutic response (FLT-PET). Therapeutic effects (FLT-PET) were observed as early as 4 days after prodrug therapy. Therapeutic gene expression (FHBG-PET) correlated with therapeutic efficiency (FLT-PET). These data indicated that the strategy of imaging-guided vector application and therapy read-out will help in the development of safe and efficient gene therapy protocols for clinical application.
Lin et al. Page 1832
In order to address the question of how immune resistance of tumors emerges in the face of immunotherapy, Lin et al. generated a highly immune-resistant cancer cell line (P3) by subjecting a susceptible cancer cell line (P0/TC-1) to multiple rounds of in vivo immune selection. Microarray analysis of P0 and P3 revealed that VCAM-1 is up-regulated in the P3-resistant variant. Further analysis revealed that the ectopic expression of VCAM-1 led to a decreased number of tumor-infiltrating lymphocytes. Thus, ectopic expression of VCAM-1 by immune-resistant tumors represents a novel mechanism of escape from T cell–mediated antitumor immunity.