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Effective cancer therapy requires that a cancer be more susceptible to a treatment than are the essential tissues in the body. A paper by Sarosiek et al. in this issue now shows that, unlike those of cancer cells, mitochondria in many tissues in adults are in an apoptosis-resistant state. [ABSTRACT FROM AUTHOR]

Clinical practice reveals that therapy with angiogenesis inhibitors often does not prolong survival of cancer patients for more than months, because tumors elicit evasive resistance. In this issue of Cancer Cell, two papers report that VEGF inhibitors reduce primary tumor growth but promote tumor invasiveness and metastasis. These perplexing findings help to explain resistance to these drugs but raise pertinent questions of how to best treat cancer patients with antiangiogenic medicine in the future. We discuss here how VEGF inhibitors can induce such divergent effects on primary tumor growth and metastasis. [Copyright &y& Elsevier]

WNT/β-catenin signaling is critical to the development of many cancer types. A paper by Mo and colleagues in a recent issue of Cell shows that autocrine CXCL12/CXCR4 chemokine signaling activates β-catenin signaling in a rare peripheral nerve sarcoma. Together with the availability of small molecules targeting CXCR4, this finding suggests new avenues for cancer therapy. [Copyright &y& Elsevier]

MYCN is an oncogenic driver of childhood neuroblastoma, a frequently lethal pediatric tumor. In a recent paper in Science Translational Medicine, Chanthery and colleagues demonstrate that PI3K inhibition leads to the dual therapeutic benefits of enhanced MYCN degradation and loss of a paracrine angiogenic signal mediated by MYCN. [Copyright &y& Elsevier]

Genetic alternations resulting in constitutive stabilization of β-catenin and altered transcription of β-catenin/TCF-regulated genes are found in many cancers. A recent Nature paper offers insights into the role of tankyrase in regulating the Wnt/β-catenin pathway and suggests that compounds targeting tankyrase''s poly-ADP-ribosylation (PARsylation) activity may hold promise for cancer therapy. [Copyright &y& Elsevier]

Cell culture studies have established NF-κB''s critical role in cancer cell survival and proliferation and led to the clinical use of NF-κB inhibitors. However, a paper in this issue of Cancer Cell reveals an anticancer function for NF-κB in a mouse model where NF-κB activity is lost specifically in hepatocytes. These studies suggest careful examination of NF-κB inhibitors as a therapeutic modality for cancer. [Copyright &y& Elsevier]

One of the most exciting developments in recent cancer treatment has been the move away from crude cytotoxic agents toward drugs that inhibit specific targets in specific cellular pathways. One assumption of this strategy is that maintenance of human cancers is dependent upon a limited cadre of therapeutically tractable oncogenic lesions. In this issue of Cancer Cell, an intriguing paper from Sharma et al. endorses this approach by showing that evolution appears to be working for us. They show that an innate asymmetry in the dynamics of intracellular signaling biases pathway inhibition in favor of cell death. This bias may significantly potentiate targeted cancer therapies. [Copyright &y& Elsevier]

Aberrant activation of the Hedgehog (Hh) signaling pathway contributes to many forms of cancer. Primary cilia are Hh signal transduction centers. Two papers in a recent issue of Nature Medicine () show that mutating cilia can increase or reduce the rates of tumorigenesis depending on how the Hh pathway is disrupted. [Copyright &y& Elsevier]