Gemcitabine and glioblastoma: challenges and current perspectives

Gemcitabine is a nucleoside analog currently used for the treatment of various solid tumors as a single agent or in combination with other chemotherapeutic drugs. Its use against highly aggressive brain tumors (glioblastoma) has been evaluated in preclinical and clinical trials leading to controversial results. Gemcitabine can inhibit DNA chain elongation, is a potent radiosensitizer and it can enhance antitumor immune activity, but it also presents some drawbacks (e.g., short half-life, side effects, chemoresistance). The aim of this review is to discuss the challenges related to the use of gemcitabine for glioblastoma and to report recent studies that suggest overcoming these obstacles opening new perspectives for its use in the field (e.g., gemcitabine derivatives and/or nanomedicines).