替莫唑胺是一種新型口服化療藥,它被廣泛用于治療惡性腦膠質(zhì)瘤。多形性膠質(zhì)母細(xì)胞瘤是IV級(jí)腦腫瘤,由異質(zhì)群體的細(xì)胞所組成,具有高度的滲透性,血管生成性及對(duì)化學(xué)治療的耐藥性等特點(diǎn)。目前標(biāo)準(zhǔn)的治療方案為術(shù)后切除放化療,但由于替莫唑胺的耐藥性,治療后只能為患者提供12~14個(gè)月的生存期?？偨Y(jié)了有關(guān)耐藥的幾種DNA修復(fù)機(jī)制及其他相關(guān)因素,揭示了一些導(dǎo)致替莫唑胺耐藥的分子機(jī)制及一些可能的治療新靶點(diǎn),同時(shí)討論了一些可能的解決方法。

Temozolomide (TMZ) is a new oral chemotherapy agent to be approved for the treatment of high-grade malignant gliomas. Glioblastoma multiform (GBM) is a grade IV brain tumor characterized by a heterogeneous population of cells that are highly infiltrative, angiogenic, and resistant to chemotherapy. The current standard of care, comprised of surgical resection followed by radiation and the chemotherapeutic agent TMZ, only provides the patients with a 12—14 month survival period post-diagnosis. In this review we will describe several DNA repairing mechanisms of drug resistance and other relevant factors. Revealing a growing number of molecular mechanisms contributing to TMZ resistance and a broad range of potentially novel targets for therapy, at the same time we discuss some possible solution.