Autophagy Modulation for Cancer Therapy
Yang et al., Page 1533
Autophagy is a catabolic process whereby damaged organelles and proteins are sequestered into autophagic vesicles, then degraded through fusion with lysosomes and reused as metabolic precursors. While autophagy can suppress tumorigenesis in normal tissues, stimulation of autophagy in established tumors promotes tumor cell survival under stressful metabolic and environmental conditions and can serve as a mechanism of treatment resistance. Yang and colleagues review the role of autophagy in cancer biology and discuss how autophagy can be exploited as a therapeutic target. While most cancer therapeutics induce autophagy, the functional consequence of autophagy induction in the context of cancer therapy continues to emerge.
Characterization of Small Molecule Inhibitors of FGFR
Squires et al., Page 1542
Fibroblast growth factor receptors (FGFR) are mutated or overexpressed in many cancers. While several agents in clinical development inhibit the kinase activity of these receptors, the cross-reactivity with other kinases prevents their use at doses that achieve fully effective blockade of FGFR receptor kinase activity. Squires and colleagues describe in detail for the first time an example of a class of next generation, selective FGFR inhibitors that are now moving into clinical development. Their preclinical studies suggest such agents will be very effective antitumor therapeutics when targeted at cancers with a molecular profile defined by FGFR pathway activation.
Aberrant Splicing of E-Cadherin
Sharma et al., Page 1751
Sharma and colleagues have identified a novel nonfunctional E-cadherin transcript that lacks exon 11 and is degraded by the nonsense-mediated decay pathway. This transcript is detected in a number of highly prevalent human cancers including breast, prostate, and head and neck cancers. As a percentage of the wild-type transcript, tumor cells express higher levels of this transcript as compared to the nonmalignant cells, indicating that this aberrant splicing is a mechanism of E-cadherin loss of function. Their studies show that overexpression of splicing factor and DNA methylation has an effect on exon 11 splicing.