An array of molecular underpinnings that dictate brain tumor growth and
progression have been unraveled over the past decades. However, brain tumors’
resistance to therapeutics remains a basic challenge, and patients with brain tumors still
face a dismal prognosis despite an application of extensive surgery, radiotherapy and
chemotherapy. Resistance mechanisms of brain tumors to chemotherapy drugs and
other kinds of therapeutic molecules range from the failure of drugs to reach their
intended sites due to physiological and pathological obstacles through to the molecular
circuitry of the cells which can be easily manipulated by cancer cells themselves.
Recent advances and knowledge in sequencing technologies of the human genome
have made it possible to perform high throughput screening of compounds libraries
against biological targets, shedding light on potential new approaches to treat brain
tumors. In this chapter, we describe the molecular characteristics of brain tumors which
will explain how cancers cleverly resist chemotherapeutics and molecularly targeted
therapies, especially focusing on the most common and lethal brain tumor in human,
glioblastoma. We then introduce many promising approaches with the preclinical and
clinical developments in brain tumor treatments to overcome, circumvent, disrupt or
manipulate the physiological and pathological barriers of brain tumors. We lastly
depict the emerging new strategies to facilitate the drug discovery through genome,
epigenome, transcriptome and proteome approaches, raising new challenges and
identifying new leads in brain tumor therapeutics.
Keywords: Biomarker, Cancer metabolism, Chemotherapy, EGFR, Electric-field
therapy, Epigenetics, Genetics, Glioblastoma, Glioma, IDH, Immunotherapy,
Molecular classification, mTOR, Targeted therapy, Temozolomide, Therapy
resistance, WHO.
