|Awarded On||February 17, 2021|
|Title||Recruitment of Established Investigators|
|Award Mechanism||Recruitment of Established Investigators|
|Institution/Organization||The University of Texas Health Science Center at San Antonio|
|Principal Investigator/Program Director||Alexander Mazin|
|Cancer Sites||All Sites|
|Summary of Goals and Objectives||
Homologous recombination (HR) is the principal pathway for the error-free repair of DNA double-strand breaks and for DNA replication fork maintenance. Mutations in BRCA1, BRCA2 and other HR genes are responsible for half of hereditary breast and ovarian cancers and increase the risk of prostate, pancreatic, and other cancers. Dysfunction in HR genes renders tumor cells addictive to alternative DNA repair pathways such that inactivation of these pathways induces synthetic lethality. Thus, development of inhibitors of PARP (PARPi) has revolutionized therapy of BRCA-deficient cancers. However, the majority of cancer patients treated with PARPi eventually develop resistance to these agents, stre...