مقالات پذیرفته شده در سومین کنگره بین المللی زیست پزشکی
Investigating Drug Resistance in HER2-Positive Breast Cancer Brain Metastases (BCBMs): New Therapeutic Approaches
Investigating Drug Resistance in HER2-Positive Breast Cancer Brain Metastases (BCBMs): New Therapeutic Approaches
Jeiran Haghighi ,1,*Mohammad Amin Dehghani ,2
1. School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 2. Student Research Committee of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Introduction: The most prevalent site of primary metastasis in patients affected with HER2-positive breast cancer undergoing treatment with HER2-targeting drugs is the brain. Thus, individuals with active breast cancer brain metastases (BCBMs) are not included in clinical trials since it is assumed that most medications do not effectively penetrate into their blood-tumor barriers.
Methods: In this study, related articles in English published in the database of PubMed were searched using the terms; HER2-positive BCBMs, HER2-targeting drugs, drug resistance, clinical trial, as well as targeted therapy.
Results: The findings revealed that limited penetration of drugs into the brain via ATP-binding cassette (ABC) transporters were possibly of clinical importance since tumor parts or rims as well as (micro) metastases located behind a functionally intact blood-brain barrier (BBB) could not be effectively eliminated using majority of existing systemic drug therapies. Brain metastasis was also considered as a major clinical challenge in the treatment of advanced breast cancer (stage IV), and assumed to be blamable for mortalities in patients. In fact, evidence found that brain-specific molecular alterations involving PI3K-AKT-mTOR pathway could cause BCBM resistance to HER2-targeted therapy implying brain-specific drug resistance mechanisms in BCBMs and a translational research paradigm to direct the development of medications for BCBM treatment.
Conclusion: It was concluded that a research strategy combining the complementary skill sets of laboratory scientists and clinical investigators using patient-derived BCBM tumor tissues in orthotopic models to ascertain context-specific resistance mechanisms could distinguish drug targets that could be exanmined in clinical trials in order to treat HER2-positive BCBMs successfully.