In Cancer Research this week, two researchers at the Kyoto University Graduate School of Medicine discuss the significance and mechanism of lymph node metastasis in cancer progression. Although the effects of local therapy like surgical lymph node dissection are not completely known, several new studies show that lymph node metastasis plays a "significant" role in the "systemic dissemination of cancer cells," the authors write. "It has been shown that chemokine receptor CXCR3 is involved in [lymph node] metastasis, and its inhibition may improve patient prognosis." It remains to be seen whether lymph node dissection is necessary to help patients achieve better survival, or if a combination of resection and radiation is enough.
Also in Cancer Research this week, researchers at the University of Utah suggest that HIF-1α confers aggressive malignant traits on human tumor cells independent of its transcriptional function. Many studies have shown that hypoxia favors tumor progression, and that hypoxia-inducible factor 1α is over-expressed in various types of cancer. "We recently identified an alternative mechanism of HIF-1α function by which HIF-1α suppresses DNA repair by counteracting c-Myc transcriptional activity that maintains gene expression," the authors write. "Here, we show that this HIF-α–c-Myc pathway plays an essential role in mediating hypoxic effects on malignant progression via genetic alterations, resulting in the formation of malignant tumors with aggressive local invasion and epithelial–mesenchymal transition."
Researchers at the Taussig Cancer Institute in Ohio investigate why current drug therapy for metastatic renal cell cancer temporarily controls the disease, but does not cure it. "Drugs that inhibit chromatin-modifying enzymes involved in transcription repression (chromatin-relaxing drugs) could have a role, by inducing apoptosis and/or through differentiation pathways," the authors write. "At low doses, the cytosine analogue decitabine can be used to deplete DNA methyl-transferase 1, modify chromatin, and alter differentiation without causing apoptosis (cytotoxicity)." The results of the study showed there may be a place for decitabine in the treatment of renal cell cancer, they add.
And finally in Cancer Research this week, a team of researchers from Australia have found that deregulated ribosomal RNA synthesis is associated with uncontrolled cancer cell proliferation, and that selective inhibitors of RNA polymerase I may offer a strategy to block cancer cell proliferation. "Coupling medicinal chemistry efforts to tandem cell- and molecular-based screening led to the design of CX-5461, a potent small-molecule inhibitor of rRNA synthesis in cancer cells," the authors write. "Our findings position CX-5461 for investigational clinical trials as a potent, selective, and orally administered agent for cancer treatment."