Potential Strategies Overcoming the Temozolomide Resistance for Glioblastoma.

Potential Strategies Overcoming the Temozolomide Resistance for Glioblastoma. Neurol Med Chir (Tokyo). 2018 Sep 21;: Authors: Jiapaer S, Furuta T, Tanaka S, Kitabayashi T, Nakada M Abstract Glioblastoma (GBM) is a highly malignant type of primary brain tumor with a high mortality rate. Although the current standard therapy consists of surgery followed by radiation and temozolomide (TMZ), chemotherapy can extend patient's post-operative survival but most cases eventually demonstrate resistance to TMZ. O6-methylguanine-DNA methyltransferase (MGMT) repairs the main cytotoxic lesion, as O6-methylguanine, generated by TMZ, can be the main mechanism of the drug resistance. In addition, mismatch repair and BER also contribute to TMZ resistance. TMZ treatment can induce self-protective autophagy, a mechanism by which tumor cells resist TMZ treatment. Emerging evidence also demonstrated that a small population of cells expressing stem cell markers, also identified as GBM stem cells (GSCs), contributes to drug resistance and tumor recurrence owing to their ability for self-renewal and invasion into neighboring tissue. Some molecules maintain stem cell properties. Other molecules or signaling pathways regulate stemness and influence MGMT activity, making these GCSs attractive therapeutic targets. Treatments targeting these molecules and pathways result in suppression of GSCs stemness and, in highly resistant cases, a decrease in MGMT activity. ...
Source: Neurologia Medico-Chirurgica - Category: Neurosurgery Tags: Neurol Med Chir (Tokyo) Source Type: research