Targeting the unfolded protein response in head and neck and oral cavity cancers.

Many FDA-approved anti-cancer therapies, targeted toward a wide array of molecular targets and signaling networks, have been demonstrated to activate the unfolded protein response (UPR). Despite a critical role for UPR signaling in the apoptotic execution of cancer cells by many of these compounds, the authors are currently unaware of any instance whereby a cancer drug was developed with the UPR as the intended target. With the essential role of the UPR as a driving force in the genesis and maintenance of the malignant phenotype, a great number of pre-clinical studies have surged into the medical literature describing the ability of dozens of compounds to induce UPR signaling in a myriad of cancer models. The focus of the current work is to review the literature and explore the role of the UPR as a mediator of chemotherapy-induced cell death in squamous cell carcinomas of the head and neck (HNSCC) and oral cavity (OCSCC), with an emphasis on preclinical studies.

Establishing a danger zone: An anatomic study of the lingual artery in base of tongue surgery.

OBJECTIVES/HYPOTHESIS: To contrast the changes in measurement of the hypoglossal/lingual artery neurovascular bundle (HLNVB) to constant surface landmarks in the base of tongue (BOT) during surgically simulated retraction versus resting anatomic position, and to identify a safe zone for BOT robotic surgery to avoid injury to the HLNVB. STUDY DESIGN: Human cadaver study. METHODS: Five fresh-frozen head and neck complexes were obtained, and seven HLNVBs were dissected. A microcaliper was used to measure the distance from the HLNVB to constant surface landmarks in resting and surgically simulated positions using a Feyh-Kastenbauer retractor. RESULTS: Measurements from foramen cecum to palatoglossus muscle (P < 0.042) was significantly different when comparing anatomical to surgically simulated positions. Importantly, the location of the lingual artery in reference to the surface landmarks measured was dramatically altered with tongue retraction. With retraction, the branches of the dorsal lingual artery were not encountered posterior to a horizontal line between midway circumvallate papilla (mCVP). CONCLUSION: Measurements of the HLNVB to surface landmarks in the BOT differs significantly between resting and a surgically simulated tongue position. The dorsal branch of the lingual artery seems more superficial in the BOT than previously described. A safe zone may exist posterior to an imaginary horizontal line between mCVP; however, further studies are needed to confirm this. LEVEL OF EVIDENCE: NA Laryngoscope, 127:110-115, 2017.