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Small molecule tyrosine kinase inhibitors in glioblastoma

Archives of Pharmacal Research 2020년 43권 4호 p.385 ~ 394
 ( Kim Ga-Young ) - Gachon University College of Pharmacy

고영탁 ( Ko Young-Tag ) - Gachon University College of Pharmacy

Abstract


Glioblastoma (GBM) is the most common malignant primary brain tumor, with poor survival despite treatment with surgery, radiotherapy, and chemotherapy with temozolomide. Little progress has been made over the last two decades, and there remain unmet medical needs. Approximately 45% of patients with GBM carry EGFR mutations, and 13% of them possess altered PDGFR genes. Moreover, VEGF/VEGFR mutations are also observed in the patient population. Tyrosine kinase inhibitors (TKIs) are emerging cancer therapy drugs that inhibit signal transduction cascades affecting cell proliferation, migration, and angiogenesis. Indications for small molecule TKIs have been successfully expanded to multiple types of cancer; however, none of the TKIs have been approved for patients with GBM. In this review, we summarize clinical trials of small molecule TKIs in patients with GBM and plausible hypotheses for negative clinical study results. We also discuss the potential TKI candidates that presented significant preclinical outcomes in patients with GBM.

키워드

Glioblastoma; Brain tumor; Small molecule drug; Tyrosine kinase inhibitor
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