The molecular genomics of metastatic brain tumours.

Abstract

INTRODUCTION Metastatic brain tumours remain an intractable clinical problem despite notable advances in the treatment of the primary cancers. It is estimated that 30-40% of breast and lung cancer patients will develop brain metastases. Typically, brain lesions are not diagnosed until patients exhibit neurological symptoms because there are currently no tests that can predict which patients will be afflicted. Brain metastases are resistant to current chemotherapies, and despite surgical resection and radiotherapy, the prognosis for these patients remains very poor with an average survival of only 6-9 months. Cancer is ultimately a genetic disease, involving patient genetics and aberrant tumour genomics; therefore the pursuit of an explanation for why or how brain metastases occur requires investigation of the associated somatic mutations. In this article, we review the current literature surrounding the molecular and genome-based mechanistic evidence to indicate driver oncogenes that hold potential biomarkers for risk, or therapeutic targets for treatment of brain metastases. CONCLUSION Patients afflicted with metastatic brain tumours are in dire need of more effective therapies, and clinicians need predictive laboratory tests to identify patients at risk of developing metastatic brain tumours. The as yet unrealized comprehensive analysis of metastatic brain tumour genomics is necessary to meet these needs. Moreover, without improved understanding of the genomic aberrations that drive metastatic brain tumours, development of biomarkers and molecularly targeted therapies will remain stalled and patient outcomes will continue to be dismal.