Protein kinase B/AKT and focal adhesion kinase: two close signaling partners in cancer

AKT (or protein kinase B) and focal adhesion kinase (FAK) are two important kinases that regulate various cellular functions. Each is overexpressed and/or aberrantly activated in diverse cancers. Several small molecular inhibitors targeting either AKT or FAK are in development or in clinical trials. It is well established that FAK is an upstream regulator of AKT signaling pathway in various cancer cell lines and in xenograft tumor models. However, very recent reports from our laboratory and others demonstrate that AKT can also directly regulate FAK through direct association and serine phosphorylation. This indicates that AKT and FAK may be dual therapeutic targets for pharmacologic intervention in the treatment of primary and metastatic cancer. FAK-AKT interaction is particularly critical for metastatic adhesion. We review recent developments in AKT and FAK signaling in cancer with the particular emphasis on the novel signaling pathways in which FAK is downstream of AKT. We also provide an update on inhibitors targeting AKT or FAK currently in clinical trials.     

Amyand hernia: what lies beneath--a proposed classification scheme to determine management

Acute appendicitis in a hernia sac occurs exceptionally. An 80-year-old male patient underwent emergency surgery for an incarcerated right inguinal hernia found to contain a gangrenous appendix. His brief improvement after an emergency herniotomy with appendectomy was followed by intestinal obstruction caused by advanced colon cancer. The unique features and individualized management of the four published types of Amyand hernia are reviewed. Rather than simply being an anatomical curiosity, Amyand hernias require individualized attention to decide how to manage both the appendix and the hernia. Clinical scrutiny, a high index of suspicion for surgical comorbidities, and a common sense approach may improve outcomes.