Frontiers in CNS Drug Discovery

Frontiers in CNS Drug Discovery

Volume: 3

Frontiers in CNS Drug Discovery is a book series devoted to publishing reviews which highlight the latest advances in drug design and discovery for disorders of the central nervous system (CNS). ...
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Molecular Targeting of Brain Tumors

Pp. 1-32 (32)

Kenta Masui, Mio Harachi, Paul S. Mischel, Tomoko Yamamoto and Noriyuki Shibata

Abstract

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.

Affiliation:

Department of Pathology, Tokyo Women’s Medical University, Tokyo 162-8666, Japan.