title: Collateral Lethality: A new therapeutic strategy in oncology.
abstract: Genomic deletion of tumor suppressor genes (TSG) is a rite of passage for virtually all human cancers. The synthetic lethal paradigm has provided a framework for the development of molecular targeted therapeutics that are functionally linked to the loss of specific TSG functions. In the course of genomic events that delete TSGs, a large number of genes with no apparent direct role in tumor promotion also sustain deletion as a result of chromosomal proximity to the target TSG. In this perspective, we review the novel concept of "collateral lethality", which has served to identify cancer-specific therapeutic vulnerabilities resulting from co-deletion of passenger genes neighboring TSG. The large number of collaterally deleted genes, playing diverse functions in cell homeostasis, offers a rich repertoire of pharmacologically targetable vulnerabilities presenting novel opportunities for the development of personalized anti-neoplastic therapies.
authors: Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Florian L
authors: FL
authors: Muller
authors: Brigham and Women's Hospital, Department of Medicine, 75 Francis Street, Boston MA 02115 USA.
authors: Elisa A
authors: EA
authors: Aquilanti
authors: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Ronald A
authors: RA
authors: DePinho