David Ljungman MD and James C Cusack Jr MD

Contents

Introduction

Chemotherapy Resistance Takes on Many Forms Altered Regulation of Apoptosis Provides Potential

Mechanism for Chemotherapy Resistance Targeting Transcription Factors to Enhance Chemotherapy

Sensitivity Future Outlook Acknowledgment References

Summary

Resistance toward chemotherapy remains one of the principle obstacles to the effective treatment of malignancies. As our knowledge of mechanisms involved in cancer biology expands, new molecular targets emerge. This chapter aims to overview the major resistance mechanisms, in order to identify potential targets appropriate for developmental therapeutics. An emphasis on the role of transcription factor NF-kB in colorectal cancer is presented as an example of how targeted therapies may advance from the bench to the bedside.

Key Words: Chemotherapy resistance; apoptosis; transcription factors; NF-kB; proteasome inhibition; combination chemotherapy.

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