CHAPTER 6 – Chemotherapy Resistance

Chemotherapy resistance can come about in a number of ways. The process by which a tumor cell becomes resistant to a particular chemotherapeutic agent is a function of the type of therapy and the phenotype of the particular tumor cell. The fact that some tumors do not respond to chemotherapy, and others rapidly recur and are often refractory to further therapy with the same or similar agents suggests that within the heterogeneous primary tumor there are cells that are intrinsically resistant to therapy. A great deal has been learned about the mechanisms of chemotherapy resistance in malignant gliomas. Despite this, there has been little impact in overall survival. Recent advances are suggesting adjuvant therapies to enhance the effectiveness of currently available therapeutic modalities by circumventing known mechanisms of resistance. Furthermore, the use of molecular analyses to predict response to specific therapies is coming into play. Microarray analyses are allowing to study changes in global gene profiles that arise as a result of therapy resistance. This will provide information on pathways that lead to chemotherapy resistance and suggest additional ways to circumvent this resistance. Despite the enormous power of modern molecular biological analyses, overcoming therapy resistance in malignant brain tumors will still require an understanding of the genotypic and phenotypic heterogeneity inherent in these tumors.