dc.contributor.author | Kaserer, T | |
dc.contributor.author | Blagg, J | |
dc.date.accessioned | 2018-09-17T09:15:13Z | |
dc.date.issued | 2018-11-15 | |
dc.identifier.citation | Cell chemical biology, 2018, 25 (11), pp. 1359 - 1371.e2 | |
dc.identifier.issn | 2451-9456 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/2693 | |
dc.identifier.eissn | 2451-9448 | |
dc.identifier.doi | 10.1016/j.chembiol.2018.07.013 | |
dc.description.abstract | The emergence of mutations that confer resistance to molecularly targeted therapeutics is dependent upon the effect of each mutation on drug affinity for the target protein, the clonal fitness of cells harboring the mutation, and the probability that each variant can be generated by DNA codon base mutation. We present a computational workflow that combines these three factors to identify mutations likely to arise upon drug treatment in a particular tumor type. The Osprey-based workflow is validated using a comprehensive dataset of ERK2 mutations and is applied to small-molecule drugs and/or therapeutic antibodies targeting KIT, EGFR, Abl, and ALK. We identify major clinically observed drug-resistant mutations for drug-target pairs and highlight the potential to prospectively identify probable drug resistance mutations. | |
dc.format | Print-Electronic | |
dc.format.extent | 1359 - 1371.e2 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Neoplasms | |
dc.subject | Mitogen-Activated Protein Kinase 1 | |
dc.subject | Antineoplastic Agents | |
dc.subject | DNA Mutational Analysis | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Mutation | |
dc.subject | Models, Molecular | |
dc.subject | Software | |
dc.subject | Small Molecule Libraries | |
dc.subject | Workflow | |
dc.subject | Molecular Targeted Therapy | |
dc.title | Combining Mutational Signatures, Clonal Fitness, and Drug Affinity to Define Drug-Specific Resistance Mutations in Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-07-26 | |
rioxxterms.versionofrecord | 10.1016/j.chembiol.2018.07.013 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-11 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cell chemical biology | |
pubs.issue | 11 | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/In Silico Medicinal Chemistry | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 1 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/In Silico Medicinal Chemistry | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 1 | |
pubs.publication-status | Published | |
pubs.volume | 25 | |
pubs.embargo.terms | No embargo | |
pubs.oa-location | https://www.sciencedirect.com/science/article/pii/S2451945618302654?via=ihub | |
icr.researchteam | In Silico Medicinal Chemistry | |
icr.researchteam | Medicinal Chemistry 1 | |
dc.contributor.icrauthor | Kaserer, Teresa | |