This chapter focuses on the components of the base excision repair (BER) pathway, the types of lesions that BER repairs, and the proteins involved in the repair process. Because BER repairs the damage caused by many anticancer agents and many BER proteins are expressed abnormally in cancers, compensatory upregulation of certain BER proteins have been implicated in contributing to chemo- and radio-resistance. It is well known that abnormal DNA damage signaling, deficiencies in DNA repair, and compensatory upregulation of DNA repair proteins are early events in tumorigenesis. Targeting key repair proteins that a tumor relies on can abolish one of the tumor’s survival advantages. Four inhibitors of BER proteins are in various stages of preclinical and clinical development: inhibitors of AP endonuclease 1 (APE1), flap endonuclease (FEN1), polymerase β, and PARP (poly-ADP ribose polymerase). A number of PARP inhibitors are already in clinical trials, and their success supports the value of pursuing other BER inhibitors as anticancer treatments.
DNA Base Excision Repair Therapeutics:Summary of Targets with a focus on APE1
VASCOTTO, Carlo;
2013-01-01
Abstract
This chapter focuses on the components of the base excision repair (BER) pathway, the types of lesions that BER repairs, and the proteins involved in the repair process. Because BER repairs the damage caused by many anticancer agents and many BER proteins are expressed abnormally in cancers, compensatory upregulation of certain BER proteins have been implicated in contributing to chemo- and radio-resistance. It is well known that abnormal DNA damage signaling, deficiencies in DNA repair, and compensatory upregulation of DNA repair proteins are early events in tumorigenesis. Targeting key repair proteins that a tumor relies on can abolish one of the tumor’s survival advantages. Four inhibitors of BER proteins are in various stages of preclinical and clinical development: inhibitors of AP endonuclease 1 (APE1), flap endonuclease (FEN1), polymerase β, and PARP (poly-ADP ribose polymerase). A number of PARP inhibitors are already in clinical trials, and their success supports the value of pursuing other BER inhibitors as anticancer treatments.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
