Strategic Developments & Future Perspective on Gene Therapy for Breast Cancer: Role of mTOR and Brk/ PTK6 as Molecular Targets.

Abstract

Breast cancer is a serious health issue and a major concern in biomedical research. Alteration in major signaling (viz. PI3K-AKT-mTOR, Ras-Raf-MEK-Erk, NF-kB, cyclin D1, JAK-STAT, Wnt, Notch, Hedgehog signaling and apoptotic pathway) contributes to the development of major subtypes of mammary carcinoma such as HER2 positive, TNBC, luminal A and B and normal-like breast cancer. Further, mutation and expression parameters of different genes involved in the growth and development of cells play an important role in the progress of different types of carcinoma, making gene therapy an emerging new therapeutic approach for the management of life-threatening diseases like cancer. The genetic targets (oncogenes and tumor suppressor genes) play a major role in the formation of a tumor. Brk/PTK6 and mTOR are two central molecules that are involved in the regulation of numerous signaling related to cell growth, proliferation, angiogenesis, survival, invasion, metastasis, apoptosis, and autophagy. Since these two proteins are highly upregulated in mammary carcinogenesis, this can be used as targeted genes for the treatment of breast cancer. However, not much work has been done on them. This review highlights the therapeutic significance of Brk and mTOR and their associated signaling in mammary carcinogenesis, which may provide a strategy to develop gene therapy for breast cancer management.