GDC-0068 Target treatment PIK3CA mutant breast cancer brain metastasis

Brain metastasis is the most common malignant secondary brain tumor in adults, and the overall survival rate of patients is very lowBreast cancer brain metastases (breast cancer brain metastases, BCBM) target ingests therapy drugs are very limitedIn recent years, second-generation sequencing technology has identified potential driver genes for brain metastatic tumors, offering hope for the treatment of BCBMIn 43%-70% of BCBM patients, phosphatidylinositol 3-Kinase 3-Kinase, PI3K pathway is activated, while phosphalycel inositol-4,5-The diphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation activates the PI3K/protein kinase B (Akt)/repamycin (mTOR) pathway, leading to abnormal proliferation of multiple tumor cells, promoting tumor progression and treating drug resistanceAtP competitive pan-Akt inhibitor GDC-0068 (ipatasertib) has demonstrated good anti-tumor activity through preclinical trials and a variety of cancer clinical trialsThe results of The Study of the Effects of GDC-0068 on Breast Cancer Brain Metastia models by Franziska Maria Ippen of the Cancer Center at Massachusetts General Hospital in the United States were published online in June 2019 in Neuro-Oncologyresearch methods
the authors first used cell activity and apoptosis analysis, cell cycle analysis, and Western blot to detect the anti-tumor effect of GDC-0068 on PIK3CA mutant and PIK3CA wild breast cancer cell lineThen, a mouse model of intracranial transplantation of PIK3CA mutant breast cancer brain metastases was established, the efficacy of GDC-0068 was analyzed in animals, and the methods of live fluorescence imaging and immunohislification were used to evaluatethe results of the studyfound that GDC-0068 reduced the cellular vitality of PIK3CA mutant breast cancer brain metastasis cell line, induced its apoptosis, inhibited phosphorylation of PRAS40 and p70 S6 kinase, and the effect was dose-dependentIn animal experiments, GDC-0068 significantly inhibited the growth of PIK3CA mutant tumors in tumor-carrying mice, which had a significant survival advantage compared to the control group, while no efficacy was found in the wild model of PIK3CATherefore, pan-Akt inhibitor GDC-0068 is a good target treatment for breast cancer brain metastasis patients with PI3K pathway activation after PIK3CA mutationPreclinical research data lay the foundation for the clinical application of GDC-0068 to treat brain metastasis.