Mechanistic insights expatiating the biological role and regulatory implications of estrogen and HER2 in breast cancer metastasis

Abstract

Breast cancer (BCa) has become the leading cause of death in women worldwide. Irrespective of advancement in cancer treatments, e.g., surgery, radiation, chemotherapy, hormonal therapy, immunotherapy, and targeted therapy, recurrence leading to metastasis poses the greatest threat in BCa management. BCa receptors estrogen (ER), progesterone (PR), and human epidermal growth factor receptor-2 (HER2) hold significant reputations as prognostic and predictive biomarkers in therapeutic decision-making. Under normal physiological conditions, these receptors modulate critical biological functions, e.g., cell migration, proliferation, and apoptosis events, etc. However, aberrant expression causes deviations, triggering signaling course to adapt permanent switching "ON" mode. The later events induce rapid and unrestrained proliferation leading to cancer. As conventional ways of cancer management ultimately lead to resistance; therefore, recently targeted therapies have been extensively studied to conquer resistance. Targeting various small molecules in downstream signaling has become an area of interest in scientific society. The severity of cancer converts many folds soon after it takes on a migratory approach that eventually commences metastasis. Cancer migration comprises protrusion of cytoplasm at the leading edge of the migration forward-facing, establishing adhesions with the basic cell-matrix, disassembly of the adhesions at the back end of the cell, and actin-myosin fiber contractions to pull the bulk of the cytoplasm forward. On the other hand, metastatic progression comprises a cascade of events, including invasion, migration, and establishment of tumor microenvironment. The progression of BCa from early stage to metastatic development causes remarkable heterogeneity. Interference at any explicit level could hamper the process, and it has thus become an area of interest for scientists. Metastasis is the ultimate cause of spreading tumor cells to invade distant organs. Recently small molecule inhibitors of protein tyrosine kinases, which can cross the blood-brain barrier, have become a center point of research for investigators in developing novel treatment strategies against BCa management.

Keywords: Biomarker; Breast cancer; Estrogen receptors; Human epidermal growth factor receptor-2; Migration; Small molecules; Tumor metastasis.