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 treat-ment. 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 meta-static 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 multi-targeted, 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. © 2020 Bentham Science Publishers.