A review on tyrosine kinase inhibitors for targeted breast cancer therapy

Vidya Sankarapandian, Ramya Lakshmi Rajendran, Conrad Ondieki Miruka, Poornima Sivamani, Balu Alagar Venmathi Maran, Rajapandiyan Krishnamoorthy, Prakash Gangadaran, Byeong-Cheol Ahn

Pathology-Research and Practice (2024), 263: 155607.

DOI: https://doi.org/10.1016/j.prp.2024.155607

Abstract

Breast cancer is a heterogeneous disease with complex molecular pathogenesis. Overexpression of several tyrosine kinase receptors is associated with poor prognosis, therefore, they can be key targets in breast cancer therapy. Tyrosine kinase inhibitors (TKIs) have emerged as leading agents in targeted cancer therapy due to their effectiveness in disrupting key molecular pathways involved in tumor growth. TKIs target various tyrosine ki­ nases, including the human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), Vascular endothelial growth factor receptor (VEGFR), anaplastic lymphoma kinase (ALK), vascular endothelial growth factor receptor (VEGFR)-associated multi-targets, rearranged during transfection (RET), fibroblast growth factor receptor (FGFR), receptor tyrosine kinase-like orphan signal 1 (ROS1), Mitogenactivated protein kinase (MAPK), and tropomyosin receptor kinase (TRK). These drugs target the tyrosine ki­ nase domain of receptor tyrosine kinases and play a vital role in proliferation and migration of breast cancer cells. Several TKIs, including lapatinib, neratinib, and tucatinib, have been developed and are currently used in clinical settings, often in combination with chemotherapy, endocrine therapy, or other targeted agents. TKIs have demonstrated remarkable benefits in enhancing progression-free and overall survival in patients with breast cancer and have become a standard of care for this population. This review provides an overview of TKIs currently being examined in preclinical studies and clinical trials, especially in combination with drugs approved for breast cancer treatment. TKIs have emerged as a promising therapeutic option for patients with breast cancer and hold potential for treating other breast cancer subtypes. The development of new TKIs and their integration into personalized treatment strategies will continue to shape the future of breast cancer therapy.

Keywords: Breast cancer, Tyrosine kinase inhibitors, Human epidermal growth factor, Chemotherapy, VEGFR, TKIs, FGFR, MAPK, HER2, ROS1, RET, TRK, Lapatinib, Neratinib, Tucatinib, Progression-free survival, Overall survival, Breast cancer treatment