NK Cell Cytotoxicity against Pediatric Tumors
Cho et al., Page 3901
Infusions of natural killer (NK) cells are being increasingly considered as a means to improve cancer therapy. Cho and colleagues sought to identify the pediatric tumor subtypes that are most susceptible to NK cell cytotoxicity. They found that Ewing sarcoma and rhabdomyosarcoma were remarkably sensitive to NK cells expanded by coculture with K562-mb15-41BBL cells. Expanded NK cells were considerably more effective than unstimulated NK cells and eradicated tumors engrafted in immunodeficient mice. These findings support a phase I clinical study testing infusions of allogeneic expanded NK cells in patients with Ewing sarcoma and rhabdomyosarcoma.
Clinical Relevance of Integrative Genomics in Breast Cancer
Parris et al., Page 3860
Treatment of breast cancer patients imposes a considerable economic burden on the health care system, and treatment selection is still primarily influenced by traditional prognostic factors. Parris and colleagues identified 12 malignancyrelated genes as molecular complements to clinicopathological features by performing microarray analysis of 97 invasive diploid breast tumors with varying clinical outcomes. The recurrent deregulation of these genes was shown to be associated with aggressive tumor behavior. In conjunction with classical features, these genes may assist in the development of new therapeutic agents and more individualized treatments.
Targeted Gene Silencing with Nanoparticles
Han et al., Page 3910
RNA interference (RNAi)-based approaches hold potential for cancer therapy, but a key challenge is the need for efficient and targeted intracellular delivery. In this study, Han and colleagues developed a novel method for targeted gene silencing using an RGD peptide linked to a chitosan nanoparticle (RGD-CH-NP). This approach increased selective delivery of siRNA and demonstrated substantial antitumor activity in orthotopic animal models of ovarian cancer. These results demonstrate that RGD-CH-NP is a highly selective delivery system for siRNA with potential for broad application in human disease.
Src Inhibition Impairs Met- Dependent Tumorigenesis
Bertotti et al., Page 3933
The activity of the Src tyrosine kinase is frequently derailed in human cancer, mainly as a consequence of oncogenic alterations in upstream regulators. Accordingly, several Src inhibitors are now being tested in phase I and phase II clinical trials. Bertotti and colleagues found that pharmacologic or genetic blockade of Src was sufficient to impair growth of gastric tumor cell lines that rely on amplification of the MET oncogene for unscheduled proliferation. This therapeutic approach holds promise for prospective diversification of treatment regimens in Met-dependent tumors, thus providing a strategy to elude or retard resistance to Met-specific inhibitors.