INTRODUCTION Tumorigenesis, a multistage, multifactorial process originating from molecular and genetic cell abnormalities, embraces extremely diverse and complex reciprocal dialogues that tumor cells and molecules engage in en route to malignancy (Al-Hajj and Clarke 2004; Balmain et al. 2003). Despite recent advances in cancer therapies, such as molecular-targeted therapy (Sawyers 2008), the clinical outcome of highly malignant tumors

CONTENTS Introduction 173 Model 176

Molecular Signaling Pathway 177 Tumor Growth Environment 177 Cell Phenotype Decision Algorithm 178

Results 179 Brain Tumor Model 179 Non-Small-Cell Lung Cancer Model 181

Discussion and Future Directions 183 Acknowledgments 187 References 187

(such as gliomas and non-small-cell lung cancer (NSCLC)) remains disappointing, with one in four deaths in the United States attributed to this disease (Jemal et al. 2009). New discoveries in cancer prevention,early detection, and treatment are therefore desperately needed.