A Mini-review on HER2 Positive Breast Cancer and its Metastasis: Resistance and Treatment Strategies

Abstract

HER2 positive breast cancer is an aggressive breast cancer followed by brain metastasis, which emerges at the later stage of breast cancer or after a few years of treatment. HER2+ breast cancer brain metastasis is a complex fatal disease with short survival and resistance to first-line drugs such as Trastuzumab, lapatinib, etc. The resistance can be due to the upregulation/downregulation of various proteins of downstream pathways mainly PI3K/AKT pathway and MAPK pathway. In addition, the Blood-brain Barrier (BBB) and Blood Tumor Barrier (BTB) also hinder the delivery to brain metastases. Thus controlling the altered proteins of the downstream pathway can be a targeted approach to control breast cancer and its brain metastasis. At the same time, targeted delivery to metastatic sites can give a synergistic effect in controlling brain metastasis and increasing the survival period. Various type of targeted nanocarriers such as single, dual, or multitargeted, pH specific, or stimuli sensitive nanocarriers can be employed for providing specific delivery to HER2+ cancer cells. Furthermore, combinations such as Trastuzumab with tyrosine kinase inhibitors (lapatinib, neratinib, afatinib), chemotherapeutic drugs (paclitaxel, doxorubicin, capecitabine), or some natural compounds (curcumin, Lycorine, berberine) with anti-apoptotic activity can provide an additional effect in the management of HER2 positive breast cancer and its metastasis.