BIRTH OF A GLYCOTHERAPY FOR BREAST CANCER.

Abstract

Breast cancer is the most common malignant disease in women and is worldwide. The incidence rate of women's breast cancer in 2020 was 2,261,419 and 2022 estimates diagnosing 1,918,030 cases. The disease is heterogeneous and the pathogenesis of breast cancer still remains unclear. Much progress has been made in early detection and better treatment to improve survival. Unfortunately, the current treatment strategies destroy the patient's quality of life. The patients develop drug resistance, exhibit severe side effects, and not afford the cost creates anxiety among the patients, families, and friends. In addition, a considerable number of patients relapse as a result of organ metastasis, e.g., the triple-negative breast cancer (TNBC, ER^-/PR^-HER2^-). The 5-year survival rate of patients who recurred with distant metastasis is less than 20%. More than half a million women worldwide still suffer from metastatic breast cancer annually, and 90% of their deaths could be attributed to metastasis. One of the reasons for the failure of cancer therapeutics is the approaches did not consider the cancer holistically. All breast cancer cells and their micro environmental capillary endothelial cells express asparagine-linked (N-linked) glycoproteins. We have tested a biologic and a small molecule, Tunicamycin-P (P = pure N-glycosylation inhibitor) to interfere with the protein N-glycosylation pathway in the endoplasmic reticulum (ER) by specifically blocking the catalytic activity of N-acetylglusosaminyl 1-phosphate transferase (GPT) activity. The outcome has been quantitative inhibition of in vitro and in vivo angiogenesis and the breast tumor progression of multiple subtypes in pre-clinical mouse models with "zero" toxicity. We have, therefore, concluded that Tunicamycin-P is expected to supersede the current therapeutics and become a Glycotherapy treating breast cancer of all subtypes.