Systematic Mapping of Kinase Addiction Combinations in Breast Cancer Cells by Integrating Drug Sensitivity and Selectivity Profiles

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Systematic Mapping of Kinase Addiction Combinations in Breast Cancer Cells by Integrating Drug Sensitivity and Selectivity Profiles. / Szwajda, Agnieszka; Gautam, Prson; Karhinen, Leena; Jha, Sawan Kumar; Saarela, Jani; Shakyawar, Sushil; Turunen, Laura; Yadav, Bhagwan; Tang, Jing; Wennerberg, Krister; Aittokallio, Tero.

In: Chemistry & Biology, Vol. 22, No. 8, 20.08.2015, p. 1144-55.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Szwajda, A, Gautam, P, Karhinen, L, Jha, SK, Saarela, J, Shakyawar, S, Turunen, L, Yadav, B, Tang, J, Wennerberg, K & Aittokallio, T 2015, 'Systematic Mapping of Kinase Addiction Combinations in Breast Cancer Cells by Integrating Drug Sensitivity and Selectivity Profiles', Chemistry & Biology, vol. 22, no. 8, pp. 1144-55. https://doi.org/10.1016/j.chembiol.2015.06.021

APA

Szwajda, A., Gautam, P., Karhinen, L., Jha, S. K., Saarela, J., Shakyawar, S., Turunen, L., Yadav, B., Tang, J., Wennerberg, K., & Aittokallio, T. (2015). Systematic Mapping of Kinase Addiction Combinations in Breast Cancer Cells by Integrating Drug Sensitivity and Selectivity Profiles. Chemistry & Biology, 22(8), 1144-55. https://doi.org/10.1016/j.chembiol.2015.06.021

Vancouver

Szwajda A, Gautam P, Karhinen L, Jha SK, Saarela J, Shakyawar S et al. Systematic Mapping of Kinase Addiction Combinations in Breast Cancer Cells by Integrating Drug Sensitivity and Selectivity Profiles. Chemistry & Biology. 2015 Aug 20;22(8):1144-55. https://doi.org/10.1016/j.chembiol.2015.06.021

Author

Szwajda, Agnieszka ; Gautam, Prson ; Karhinen, Leena ; Jha, Sawan Kumar ; Saarela, Jani ; Shakyawar, Sushil ; Turunen, Laura ; Yadav, Bhagwan ; Tang, Jing ; Wennerberg, Krister ; Aittokallio, Tero. / Systematic Mapping of Kinase Addiction Combinations in Breast Cancer Cells by Integrating Drug Sensitivity and Selectivity Profiles. In: Chemistry & Biology. 2015 ; Vol. 22, No. 8. pp. 1144-55.

Bibtex

@article{262e03a3b6974ccd89609f753e905c2c,

title = "Systematic Mapping of Kinase Addiction Combinations in Breast Cancer Cells by Integrating Drug Sensitivity and Selectivity Profiles",

abstract = "Chemical perturbation screens offer the possibility to identify actionable sets of cancer-specific vulnerabilities. However, most inhibitors of kinases or other cancer targets result in polypharmacological effects, which complicate the identification of target dependencies directly from the drug-response phenotypes. In this study, we developed a chemical systems biology approach that integrates comprehensive drug sensitivity and selectivity profiling to provide functional insights into both single and multi-target oncogenic signal addictions. When applied to 21 breast cancer cell lines, perturbed with 40 kinase inhibitors, the subtype-specific addiction patterns clustered in agreement with patient-derived subtypes, while showing considerable variability between the heterogeneous breast cancers. Experimental validation of the top predictions revealed a number of co-dependencies between kinase targets that led to unexpected synergistic combinations between their inhibitors, such as dasatinib and axitinib in the triple-negative basal-like HCC1937 cell line. ",

keywords = "Apoptosis/drug effects, Breast Neoplasms/drug therapy, Cell Line, Tumor, Cell Proliferation/drug effects, Computer Simulation, Drug Resistance, Neoplasm, Female, Humans, Protein Kinase Inhibitors/pharmacology, Systems Biology/methods",

author = "Agnieszka Szwajda and Prson Gautam and Leena Karhinen and Jha, {Sawan Kumar} and Jani Saarela and Sushil Shakyawar and Laura Turunen and Bhagwan Yadav and Jing Tang and Krister Wennerberg and Tero Aittokallio",

year = "2015",

month = aug,

day = "20",

doi = "10.1016/j.chembiol.2015.06.021",

language = "English",

volume = "22",

pages = "1144--55",

journal = "Chemistry and Biology",

issn = "2451-9448",

publisher = "Elsevier",

number = "8",

}

RIS

TY - JOUR

T1 - Systematic Mapping of Kinase Addiction Combinations in Breast Cancer Cells by Integrating Drug Sensitivity and Selectivity Profiles

AU - Szwajda, Agnieszka

AU - Gautam, Prson

AU - Karhinen, Leena

AU - Jha, Sawan Kumar

AU - Saarela, Jani

AU - Shakyawar, Sushil

AU - Turunen, Laura

AU - Yadav, Bhagwan

AU - Tang, Jing

AU - Wennerberg, Krister

AU - Aittokallio, Tero

PY - 2015/8/20

Y1 - 2015/8/20

N2 - Chemical perturbation screens offer the possibility to identify actionable sets of cancer-specific vulnerabilities. However, most inhibitors of kinases or other cancer targets result in polypharmacological effects, which complicate the identification of target dependencies directly from the drug-response phenotypes. In this study, we developed a chemical systems biology approach that integrates comprehensive drug sensitivity and selectivity profiling to provide functional insights into both single and multi-target oncogenic signal addictions. When applied to 21 breast cancer cell lines, perturbed with 40 kinase inhibitors, the subtype-specific addiction patterns clustered in agreement with patient-derived subtypes, while showing considerable variability between the heterogeneous breast cancers. Experimental validation of the top predictions revealed a number of co-dependencies between kinase targets that led to unexpected synergistic combinations between their inhibitors, such as dasatinib and axitinib in the triple-negative basal-like HCC1937 cell line.

AB - Chemical perturbation screens offer the possibility to identify actionable sets of cancer-specific vulnerabilities. However, most inhibitors of kinases or other cancer targets result in polypharmacological effects, which complicate the identification of target dependencies directly from the drug-response phenotypes. In this study, we developed a chemical systems biology approach that integrates comprehensive drug sensitivity and selectivity profiling to provide functional insights into both single and multi-target oncogenic signal addictions. When applied to 21 breast cancer cell lines, perturbed with 40 kinase inhibitors, the subtype-specific addiction patterns clustered in agreement with patient-derived subtypes, while showing considerable variability between the heterogeneous breast cancers. Experimental validation of the top predictions revealed a number of co-dependencies between kinase targets that led to unexpected synergistic combinations between their inhibitors, such as dasatinib and axitinib in the triple-negative basal-like HCC1937 cell line.

KW - Apoptosis/drug effects

KW - Breast Neoplasms/drug therapy

KW - Cell Line, Tumor

KW - Cell Proliferation/drug effects

KW - Computer Simulation

KW - Drug Resistance, Neoplasm

KW - Female

KW - Humans

KW - Protein Kinase Inhibitors/pharmacology

KW - Systems Biology/methods

U2 - 10.1016/j.chembiol.2015.06.021

DO - 10.1016/j.chembiol.2015.06.021

M3 - Journal article

C2 - 26211361

VL - 22

SP - 1144

EP - 1155

JO - Chemistry and Biology

JF - Chemistry and Biology

SN - 2451-9448

IS - 8

ER -

ID: 199428342

Forskning