Advances in the biology of astrocytomas : Current Opinion in Neurology (original) (raw)

Neoplasms

aWestern Hospital and bArthur & Sonia Labatts Brain Tumor Center, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

Correspondence to Abhijit Guha MSc, MD, FRCS(C), FACS, Professor of Surgery (Neurosurgery), Alan & Susan Hudson Chair in Neurooncology, 4W-446, Western Hospital, 399 Bathurst St, Toronto M5T 2S8, Ontario, Canada Tel: Clinical: 416-603-5740 Lab: 416-813-6688; fax: Clinical: 416-603-5298; Lab: 416-813-8456; Cell: 416-951-9354; e-mail: [email protected]

Abbreviations

COX-2: cyclooxygenase-2

CTMP: carboxyl-terminal modulator protein

EC: endothelial cell

EGF: epidermal growth factor

EGFR: epidermal growth factor receptor

FAK: focal adhesion kinase

FasL: Fas ligand

GBM: Grade-IV glioblastoma multiforme

GEM: genetically engineered model

iNOS: inducible nitric oxide synthetase

LRP: lung resistance protein

MGMT: O6 methylguanine-DNA methyltransferase

MMP: metalloprotease

MRP1: multi-drug resistance protein

MVD: microvascular density

Pgp: P-glycoprotein

PTTG: pituitary tumor transforming gene

SVZ: sub-ventricular zone

TIMP: tissue inhibitor

VEGF: vascular endothelial growth factor

Abstract

Purpose of review

Conventional surgery, radio- and chemotherapy have failed to significantly improve the prognosis of patients with malignant astrocytomas - hence the need for understanding their molecular biology. Harvesting this understanding to yield novel biological targeted therapies has approached the clinical doorstep. Therapeutic efficacy will likely require combinatorial therapy involving biologicals and conventional therapies, with small incremental efficacy in selected sub-groups. This review highlights some of the findings over the past year (June 2003-2004) that have contributed to this slow but essential journey towards our understanding of the biology of astrocytomas.

Recent findings

The accumulation of loss and/or gain of function molecular alterations underlying astrocytoma formation, progression and key growth parameters including proliferation, angiogenesis, apoptosis, invasion and resistance are emerging. These alterations involve those regulating the growth factor/receptor and downstream signaling networks, cell cycle, immune modulators and other key biological processes. The advances are facilitated by interactions amongst clinician and basic scientists, in both academia and industry. They have incorporated high-throughput bioinformatics analysis of genomic and expression array data, the emerging field of proteomics and development of various genetically engineered models of astrocytomas.

Summary

Astrocytomas, like other cancers, are a result of several molecular alterations, some of which strongly correlate to their pathological grade. However, molecular heterogeneity exists between astrocytomas of similar grades and likely between varying micro-environmental regions of a single tumor. Characterization of the molecular signature of an astrocytoma and linking with the appropriate ‘tailored’ therapie(s) is the hope of the future.