title: Drugging the addict: non-oncogene addiction as a target for cancer therapy.
abstract: Historically, cancers have been treated with chemotherapeutics aimed to have profound effects on tumor cells with only limited effects on normal tissue. This approach was followed by the development of small-molecule inhibitors that can target oncogenic pathways critical for the survival of tumor cells. The clinical targeting of these so-called oncogene addictions, however, is in many instances hampered by the outgrowth of resistant clones. More recently, the proper functioning of non-mutated genes has been shown to enhance the survival of many cancers, a phenomenon called non-oncogene addiction. In the current review, we will focus on the distinct non-oncogenic addictions found in cancer cells, including synthetic lethal interactions, the underlying stress phenotypes, and arising therapeutic opportunities.
authors.affiliation: Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Remco
authors.initials: R
authors.lastname: Nagel
authors.affiliation: Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Semenova
authors.affiliation: Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands a.berns@nki.nl.
authors.forename: Anton
authors.identifier: 0000-0003-2194-1988
authors.initials: A
authors.lastname: Berns
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D009857:Oncogenes; D013312:Stress, Physiological; D000072020:Synthetic Lethal Mutations
keywords: cancer; non‐oncogene addiction; synthetic lethality; therapy; vulnerability