Applying Synthetic Lethality for the Selective Targeting of Cancer
Synthetic lethality refers to the requirement that two defects be present for cell death to occur. When an agent damages DNA, its effects on the cell can be amplified if the efforts of the cell to repair the damage are inhibited. Clinical application of this idea is just beginning. The development o...
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| Published in | The New England journal of medicine Vol. 371; no. 18; pp. 1725 - 1735 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
Waltham, MA
Massachusetts Medical Society
30.10.2014
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Synthetic lethality refers to the requirement that two defects be present for cell death to occur. When an agent damages DNA, its effects on the cell can be amplified if the efforts of the cell to repair the damage are inhibited. Clinical application of this idea is just beginning.
The development of anticancer treatments that are largely selective for the neoplastic clone has, until recently, remained an elusive goal. However, an expanding cadre of “targeted therapeutics” in clinical use illustrates the enormous potential of this approach. Genetic alterations in cancer in humans may involve gene activation, amplification, or inactivation or allelic haplodeficiency. These signature genetic features that are unique to the malignant clone can be exploited to develop treatments that are inherently tumor-specific.
The concept of synthetic lethality originates from studies in drosophila model systems in which a combination of mutations in two or more separate genes leads to . . . |
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| AbstractList | Synthetic lethality refers to the requirement that two defects be present for cell death to occur. When an agent damages DNA, its effects on the cell can be amplified if the efforts of the cell to repair the damage are inhibited. Clinical application of this idea is just beginning. Synthetic lethality refers to the requirement that two defects be present for cell death to occur. When an agent damages DNA, its effects on the cell can be amplified if the efforts of the cell to repair the damage are inhibited. Clinical application of this idea is just beginning. The development of anticancer treatments that are largely selective for the neoplastic clone has, until recently, remained an elusive goal. However, an expanding cadre of “targeted therapeutics” in clinical use illustrates the enormous potential of this approach. Genetic alterations in cancer in humans may involve gene activation, amplification, or inactivation or allelic haplodeficiency. These signature genetic features that are unique to the malignant clone can be exploited to develop treatments that are inherently tumor-specific. The concept of synthetic lethality originates from studies in drosophila model systems in which a combination of mutations in two or more separate genes leads to . . . |
| Author | McLornan, Donal P Mufti, Ghulam J List, Alan |
| Author_xml | – sequence: 1 givenname: Donal P surname: McLornan fullname: McLornan, Donal P organization: From King's College Hospital NHS Foundation Trust, London (D.P.M., G.J.M.); and Moffitt Cancer Center, Tampa, FL (A.L.) – sequence: 2 givenname: Alan surname: List fullname: List, Alan organization: From King's College Hospital NHS Foundation Trust, London (D.P.M., G.J.M.); and Moffitt Cancer Center, Tampa, FL (A.L.) – sequence: 3 givenname: Ghulam J surname: Mufti fullname: Mufti, Ghulam J organization: From King's College Hospital NHS Foundation Trust, London (D.P.M., G.J.M.); and Moffitt Cancer Center, Tampa, FL (A.L.) |
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| Snippet | Synthetic lethality refers to the requirement that two defects be present for cell death to occur. When an agent damages DNA, its effects on the cell can be... |
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| SubjectTerms | Antineoplastic Agents - therapeutic use Apoptosis Biological and medical sciences Cancer Cell death Deoxyribonucleic acid DNA DNA Repair Drug Discovery General aspects Genes, Lethal Genes, myc Humans Kinases Lethality Medical sciences Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Mutation Neoplasms - genetics Neoplasms - therapy Poly(ADP-ribose) Polymerase Inhibitors Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins p21(ras) ras Proteins - genetics Tumors |
| Title | Applying Synthetic Lethality for the Selective Targeting of Cancer |
| URI | https://nejm.org/doi/full/10.1056/NEJMra1407390 https://www.ncbi.nlm.nih.gov/pubmed/25354106 https://www.proquest.com/docview/1618914485 https://search.proquest.com/docview/1619314639 |
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