Brain tumors are most aggressive lethal types of cancer and have been
reported to have poor prognosis. Patients diagnosed with glioblastoma multiforme
(GBM) have an aggressive, tough and resistant brain tumor with average survival 12 to
16 months. The most common age for diagnosis of GBM is reported to be in between
45 and 70 years. GBM arises from glial cells which are glue like supportive cells of the
brain that help to maintain and protect the neurons of central and peripheral nervous
system from any damage.
GBM is usually treated with surgery and radiation followed by chemotherapy where
temozolomide (TMZ) is a part of therapy. TMZ is an alkaline agent that destroys the
glioblastoma cells by forming O6-methylgunine in DNA. TMZ is an anticancer drug
popularly used sometimes along with ionizing radiation. However, one of the
downsides of chemotherapy is the development of resistance against the drug which
results in the failure of the treatment and hence poor prognosis. The alternate treatment
strategies are being explored to prolong the survival of GBM. The treatment of GBM
by using HDACi (histone deacetylase inhibitors), MGMT (O6-methylguanine DNA
methyltransferase) inhibitors, beta blockers, statins, antimetabolites, and some phytotherapeutics
in synergistic combinations may be beneficial for outcome. A number of
drugs are being investigated in synergistic combination and will offer a substantial
survival advantage in GBM patients. The present chapter discusses the synergistic
combinations of mainly TMZ with various other anti-cancer or FDA approved drugs
for other indications that can enhance different molecular mechanisms, increase cell
death, reduce drug resistance or decrease the drug toxicity in glioblastomas.
Keywords: Bcl-2, Cancer Stem Cells, Chemotherapeutics, Combination, GBM,
Hypoxia, MGMT, Resistance, Temozolomide, Therapy.
