Preface

Chapter 6 **Alterations in TP53 gene – Implications in Tumorigenesis**

Anselmo and Edivaldo Herculano C. de Oliveira

**Section 4 Angiogenesis and Immune Therapy – New Therapeutical**

Chapter 7 **Anti-Angiogenesis, Gene Therapy, and Immunotherapy in**

Chapter 8 **Erlotinib in Glioblastoma – A Current Clinical Perspective 223**

**Section 5 New Drugs for CNS Tumors – The Hope for the Future 237**

Chapter 9 **Comparative Preclinical Pharmacology and Toxicology for 4-**

**(GBM) and Metastatic Cancers Involving the Central**

Melody Luttrell, Edward Stevens and Rodger Thompson

Georg Karpel-Massler and Marc-Eric Halatsch

**Approaches 175**

**VI** Contents

**Malignant Gliomas 177**

Hassan M Fathallah-Shaykh

**Nervous System 239**

**Process and Prognosis in Central Nervous System Cancer 127** Igor Andrade Pessôa, Fabio P. Estumano da Silva, Nilson Praia

Paula Province, Alexis Bashinski Shaefer, Benjamin McCullough and

**demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) — A Potential Neuro-Alkylating Agent for Glioblastoma**

Lee Roy Morgan, Andrew H. Rodgers, Gerard Bastian, Edmund Benes, William S. Waud, Christopher Papagiannis, Dan Krietlow, Branko S. Jursic, Robert F. Struck, Gerald LaHoste, Melissa Thornton, The treatment of malignancies involving the central nervous system – primary, as well as meta‐ static, has improved in recent years, however, the long term responses are still depressing.

The causes for the paucity of useful chemotherapeutic agents have been due to a reluctance to enroll patients with advanced CNS cancer in new clinical trials.

Thus, the knowledge of anti-cancer drug pharmacology in the brain is lagging. *Tumors of the Central Nervous System – Primary and Secondary* presents a concerted effort to appreciate the relationships between the pathophysiology of malignancies growing in the brain, the func‐ tions of the blood brain barrier (BBB), tolerance of the brain to potential new drugs, and new imaging techniques. Neurooncology has been a sleeping giant and finally the neurosur‐ geons, neuropharmacologists, neuro-oncologists, neuro-physiologists and the medicinal chemists are all working together to identify novel, safe and effective anticancer agents and procedures to treat CNS tumors. Plus the FDA's Orphan Designated Drug program has cre‐ ated an incentive for pharmaceutical industry involvement. Maybe we can *'catch up'* .

Every chapter in "*Tumors of the Central Nervous System – Primary and Secondary* " is an exam‐ ple of neuro-collaborations and contains new approaches, in-depth discussions and/or re‐ views of diagnostic and therapeutic concepts that will improve the management of key topics in neurooncology.

Neurooncology is still an *empirical subspecialty* when it comes to selecting treatment plans or cancer chemotherapy. We continue to face the *age old question* from patients and families during the treatment process – *will the patient respond, not when a response will occur* . This is often based on the fact that we lack the ability to predict whether or not a drug or drugs will:

*Be absorbed*

*Be absorbed*

*Undergo the required activation or metabolism*

*Enter the cancer cell*

*Target a bio-sensitive site*

*and* , if all the required pharmacological criteria are met, in fact *'will the cancer cell respond in the proper way to therapy – with death'!*

*Tumors of the Central Nervous System – Primary and Secondary* is designed to integrate con‐ cepts in surgery, diagnostic imaging, radiation and molecular pharmacology with results from empirical trials to promote our advancement on current neurooncology issues.

Perhaps the information presented in these chapters will help reverse the negative concept that *'Cancer of the Brain'* always has a fatal outcome.

I sincerely hope that all enjoy reading the book, as much as I have enjoyed writing a chapter and reviewing the book.

> **Lee Roy Morgan, MD, PhD** CEO DEKK-TEC, Inc. New Orleans, United States

**Section 1**

**CNS Cancer – Past, Present and Future**

**CNS Cancer – Past, Present and Future**

Perhaps the information presented in these chapters will help reverse the negative concept

I sincerely hope that all enjoy reading the book, as much as I have enjoyed writing a chapter

**Lee Roy Morgan, MD, PhD**

New Orleans, United States

CEO

DEKK-TEC, Inc.

that *'Cancer of the Brain'* always has a fatal outcome.

and reviewing the book.

VIII Preface

**Chapter 1**

**High Grade Glioma — Standard Approach, Obstacles and**

Glioblastoma Multiforme is the most malignant of gliomas. These malignancies that arise from glial cells remain one of the pre-eminent and confounding therapeutic challenges in oncology and medicine at-large. Though uncommon, it continues to be responsible for disproportionate rates of morbidity and mortality the world over, as qualified by a median survival of only about 15 months despite optimal treatment [1, 2]. This is in large part due to its heterogeneous biology, exceedingly complex molecular pathogenesis, and the tumor's predilection for growth in the CNS. Ongoing research, particularly in the last decade, has provided the scientific and medical worlds with ever deeper insight into, and further elucidation of, the biology and molecular pathogenesis of Glioblastoma Multiforme (GBM). This in turn has led to compelling novel treatment modalities that range from rudimentarily conceptual to, excitingly, on the very cusp of implementation. This chapter aims to provide the reader with a comprehensive survey of Glioblastoma Multiforme contextualized within the broader realm of malignant gliomas. GBM is the most common malignant primary brain cancer in adults, accounting for roughly 3 new cases per 100,000 people [3]. Underscoring its importance as a therapeutic target, GBM accounts for nearly 16% of all brain tumors and, furthermore, nearly 46% of malignant gliomas [3]. The average age at diagnosis of GBM is 64 years of age, and, for reasons yet unclear, it has demonstrated a clear male predilection, being about 1.6 times more common in males than

Running in tandem with the quest for more effective therapies for GBM has been a long and intensive search for clear risk factors positively associated with the development of GBM. This search, however, has been fraught with many dead ends. Indeed, no clear inciting cause has been identified for the vast majority of cases of GBM and the only bona-fide established risk factor is exposure to ionizing radiation. The cause-effect relationship between ionizing

> © 2014 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**Future Directions**

http://dx.doi.org/10.5772/58548

**1. Introduction**

females [3].

Siddharth K. Joshi and Richard Zuniga

Additional information is available at the end of the chapter
