Benefits and Pitfalls of a Glycosylation Inhibitor Tunicamycin in the Therapeutic Implication of Cancers.

The aberrant glycosylation is a hallmark of cancer progression and chemoresistance. It is also an immune therapeutic target for various cancers. Tunicamycin (TM) is one of the potent nucleoside antibiotics and an inhibitor of aberrant glycosylation in various cancer cells, including breast cancer, gastric cancer, and pancreatic cancer, parallel with the inhibition of cancer cell growth and progression of tumors. Like chemotherapies such as doxorubicin (DOX), 5'fluorouracil, etoposide, and cisplatin, TM induces the unfolded protein response (UPR) by blocking aberrant glycosylation. Consequently, stress is induced in the endoplasmic reticulum (ER) that promotes apoptosis. TM can thus be considered a potent antitumor drug in various cancers and may promote chemosensitivity. However, its lack of cell-type-specific cytotoxicity impedes its anticancer efficacy. In this review, we focus on recent advances in our understanding of the benefits and pitfalls of TM therapies in various cancers, including breast, colon, and pancreatic cancers, and discuss the mechanisms identified by which TM functions. Finally, we discuss the potential use of nano-based drug delivery systems to overcome non-specific toxicity and enhance the therapeutic efficacy of TM as a targeted therapy.

Increased Incidence of Thrombotic Complications With Non-small Cell Lung Cancer Necessitates Consideration of Prophylactic Anticoagulation in Young Individuals.

Venous thromboembolism (VTE) is a common complication in cancer patients and is associated with increased morbidity and mortality. Lung cancer is commonly associated with VTE including pulmonary embolism. We did a retrospective analysis from the 2013 Healthcare Cost and Utilization Project data to determine the role of age as a factor in the development of VTE in this patient group. Patients were selected using the International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes for metastatic lung cancer and VTE. The patients were stratified by age, sex, race/ethnicity, and site of VTE. There was a total of 16,577 VTE events detected out of a total of 182,863 cases of metastatic lung cancer, representing 9% of the total cases. In patients under 65 years of age, there were 356.82 more cases of pulmonary embolism per 100,000 individuals compared to those older than 65 years (p<0.0001). The same age group also showed 374.83 more upper extremity VTE, 286.94 more non-pulmonary thoracic VTE, and 263.97 more abdominal VTE events per 100,000 individuals (p<0.0001). In conclusion, we found that patients under the age of 65 years had a significantly higher incidence of VTE, pulmonary embolism, upper extremity VTE as well as abdominal and non-pulmonary VTE.