Tyrosine Kinase Inhibitors in the Combination Therapy of HER2 Positive Breast Cancer

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) accounts for about 20% to 30% of all BC subtypes and is characterized by invasive disease and poor prognosis. With the emergence of anti-HER2 target drugs, HER2-positive BC patient outcomes have changed dramatically. However, treatment failure is mostly due to drug resistance and the special treatment needs of different subgroups. Small molecule tyrosine kinase inhibitors can inhibit multiple targets of the human epidermal growth factor receptor family and activate PI3K/AKT, MAPK, PLC gamma, ERK1/2, JAK/STAT, and other pathways affecting the expression of MDM2, mTOR, p27, and other transcription factors. This can help regulate the differentiation, apoptosis, migration, growth, and adhesion of normal cells and reverse drug resistance to a certain extent. These inhibitors can cross the blood-brain barrier and be administered orally. They have a good synergistic effect with effective drugs such as trastuzumab, pertuzumab, t-dm1, and cyclin-dependent kinase 4 and 6 inhibitors. These advantages have resulted in small-molecule tyrosine kinase inhibitors attracting attention. The new small-molecule tyrosine kinase inhibitor was investigated in multi-target anti-HER2 therapy, showed a good effect in preclinical and clinical trials, and to some extent, improved the prognosis of HER2-positive BC patients. Its use could lead to a de-escalation of treatment in some patients, possibly preventing unnecessary procedures along with the associated side effects and costs.