American Association for Cancer Research

June 2008 Molecular Cancer Therapeutics Highlights

PDF Version for Printing pdf4.gif

Selected Articles from the June 1, 2008 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Molecular Cancer Therapeutics is published. Click on the article title to view the complete article.

View the Table of Contents for the June 2008 issue of Molecular Cancer Therapeutics


RHBDF1 Function Is Essential To Epithelial Cancer Growth

Yan et al.

Page 1355

Little is known about the function of the human rhomboid family-1 gene (RHBDF1). Yan and colleagues found that silencing the RHBDF1 gene with siRNA resulted in apoptosis in breast cancer MDA-MB-435 cells and autophagy in head and neck squamous cell cancer 1483 cells. The treatment also led to significant down-modulation of activated AKT and ERK in the cells. Furthermore, silencing the RHBDF1 gene in MDA-MB-435 or 1483 xenograft tumors on athymic nude mice resulted in marked inhibition of tumor growth. Their findings indicated that RHBDF1 has a pivotal role in sustaining growth signals in epithelial cancer cells.


COX-2 Inhibitors Upregulate CRMP-1 Expression

Wu et al.

Page 1365

Collapsin response mediator protein 1 (CRMP-1) controls neural development and axonal growth, but also acts as a cancer invasion suppressor. Wu and colleagues investigated the transcriptional regulation of CRMP-1 expression. Site-directed mutagenesis and deletion analysis revealed that the two C/EBPα sites, from nt-122 to -133 and nt-101 to -113, are the most important regulatory elements. The authors concluded that transcription of the invasion suppressor, CRMP-1, is reciprocally regulated at the promoter region by C/EBPα and SP1. COX-2 inhibitors increase CRMP-1 expression by inhibiting Sp1-DNA complex formation and enhancing DNA binding of C/EBPα at the promoter. 


Hedgehog Signaling Inhibitors Could Treat MCL

Hegde et al.

Page 1450

Altered hedgehog (Hh) signaling is involved in the pathogenesis of many types of cancer, and inhibitors of Hh signaling are being evaluated in clinical trials to improve therapy. However, the role of Hh signaling in the pathogenesis of mantle cell lymphoma (MCL) is not known. Hegde and colleagues have shown that Hh-signaling through the GLI transcription factor complex is involved in the pathogenesis of MCL. Targeting of GLI using antisense oligonucleotides not only inhibited the proliferation of MCL cells but also rendered them more susceptible to chemotherapy by down-regulating bcl2 and cyclin D1, providing powerful evidence to support clinical trials to establish the value of Hh signaling inhibition in the treatment of MCL.


Rituxan, an anti-CD20 monoclonal antibody that depletes B cells by targeting the antigen CD20, has been clinically used for B cell-related hematological malignancies, autoimmune diseases and other disorders. However, the complicated manufacturing procedure, high costs, and short half-life of Rituxan in sera heavily limit its wide-spread applications. Chen and colleagues generated a recombinant adenovirus that encodes the Rituxan gene and generates high levels of full-length functional monoclonal anti-CD20 antibody in vivo. A single administration of the adenovirus led a continuous B cell deletion in cynomolgus monkeys for at least 70 days. Thus, the anti-CD20 antibody expressing adenovirus may be used as a potential anti-CD20 gene therapy system for the treatment of B cell-related malignant disorders.


CD44 Supports Trafficking of Normal and Malignant Cells

Wallach-Dayan et al.

Page 1615

Therapeutic targeting of a CD44 variant preferentially expressed on cancer cells may spare cells engaged in normal physiological functions. Wallach-Dayan and colleagues showed the advantage of gene vaccination against mammary tumor with a novel medical tubular device mimicking a lymph node (termed virtual lymphnode; VLN), which was loaded with specific CD44 variant (CD44v) cDNA and inserted under the mouse skin. Antigen presenting cells penetrating into the VLN translate the cDNA to cell surface CD44 and present it to lymphocytes, resulting in anti-CD44v antibody production. The vaccinated mice developed resistance to a tumor expressing the corresponding CD44 variant.


Top