Cited by 134Cancer-related Molecular PathwaysCancer Genomics and DiagnosticsChromatin Remodeling and Cancer

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Collateral Lethality: A New Therapeutic Strategy in Oncology

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Muller, Florian L., Aquilanti, Elisa A., DePinho, Ronald A.·2015·Trends in Cancer

DOI 10.1016/j.trecan.2015.10.002PMC PMC4746004

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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.

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Authors: Muller, F. L., Aquilanti, E. A., & DePinho, R. A.
Affiliations: Brigham and Women's Hospital (US)
The University of Texas MD Anderson Cancer Center (US)
Corresponding author: DePinho, Ronald A.
ORCID: Aquilanti, Elisa A.
DePinho, Ronald A.
Venue: Trends in Cancer
Publisher: Elsevier BV
Published: 2015-11
Volume: 1
Issue: 3
Pages: 161-173
ISSN: 2405-8025 (ISSN-L)
2405-8033
DOI: 10.1016/j.trecan.2015.10.002
PMC: PMC4746004
OpenAlex: W2179093278
Cited by: 132
References: 116
Citations by year: 2026: 10 · 2025: 12 · 2024: 10 · 2023: 9 · 2022: 18 · 2021: 14 · 2020: 17 · 2019: 15 · 2018: 11 · 2017: 10 · 2016: 6
FWCI: 0.97
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in cancer (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Cancer Institute (P01CA095616, P50CA127001)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: synthetic lethality, tumor suppressor, passenger genes, precision oncology, targeted cancer therapy

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Collateral Lethality: A New Therapeutic Strategy in Oncology

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