Disentangling ERBB signaling in breast cancer subtypes: a model-based Analysis
Targeted therapies have shown striking success in the treatment of cancer over the last years. However, their specific effects on an individual tumor appear to be varying and difficult to predict. Using an integrative modeling approach that combines mechanistic and regression modeling, we gained ins...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
12 May 2022
|
| In: |
Cancers
Year: 2022, Jahrgang: 14, Heft: 10, Pages: 1-24 |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers14102379 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers14102379 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/14/10/2379 
|
| Verfasserangaben: | Svenja Kemmer, Mireia Berdiel-Acer, Eileen Reinz, Johanna Sonntag, Nooraldeen Tarade, Stephan Bernhardt, Mirjam Fehling-Kaschek, Max Hasmann, Ulrike Korf, Stefan Wiemann and Jens Timmer |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1810175704 | ||
| 003 | DE-627 | ||
| 005 | 20250109050534.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 220714s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/cancers14102379 |2 doi | |
| 035 | |a (DE-627)1810175704 | ||
| 035 | |a (DE-599)KXP1810175704 | ||
| 035 | |a (OCoLC)1341463902 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 32 |2 sdnb | ||
| 100 | 1 | |a Kemmer, Svenja |e VerfasserIn |0 (DE-588)126248958X |0 (DE-627)1810179602 |4 aut | |
| 245 | 1 | 0 | |a Disentangling ERBB signaling in breast cancer subtypes |b a model-based Analysis |c Svenja Kemmer, Mireia Berdiel-Acer, Eileen Reinz, Johanna Sonntag, Nooraldeen Tarade, Stephan Bernhardt, Mirjam Fehling-Kaschek, Max Hasmann, Ulrike Korf, Stefan Wiemann and Jens Timmer |
| 264 | 1 | |c 12 May 2022 | |
| 300 | |a 24 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 14.07.2022 | ||
| 520 | |a Targeted therapies have shown striking success in the treatment of cancer over the last years. However, their specific effects on an individual tumor appear to be varying and difficult to predict. Using an integrative modeling approach that combines mechanistic and regression modeling, we gained insights into the response mechanisms of breast cancer cells due to different ligand-drug combinations. The multi-pathway model, capturing ERBB receptor signaling as well as downstream MAPK and PI3K pathways was calibrated on time-resolved data of the luminal breast cancer cell lines MCF7 and T47D across an array of four ligands and five drugs. The same model was then successfully applied to triple negative and HER2-positive breast cancer cell lines, requiring adjustments mostly for the respective receptor compositions within these cell lines. The additional relevance of cell-line-specific mutations in the MAPK and PI3K pathway components was identified via L1 regularization, where the impact of these mutations on pathway activation was uncovered. Finally, we predicted and experimentally validated the proliferation response of cells to drug co-treatments. We developed a unified mathematical model that can describe the ERBB receptor and downstream signaling in response to therapeutic drugs targeting this clinically relevant signaling network in cell line that represent three major subtypes of breast cancer. Our data and model suggest that alterations in this network could render anti-HER therapies relevant beyond the HER2-positive subtype. | ||
| 650 | 4 | |a breast cancer | |
| 650 | 4 | |a ERBB signaling | |
| 650 | 4 | |a mathematical modeling | |
| 650 | 4 | |a signal transduction | |
| 650 | 4 | |a systems biology | |
| 650 | 4 | |a targeted therapy | |
| 700 | 1 | |a Berdiel-Acer, Mireia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Reinz, Eileen |e VerfasserIn |0 (DE-588)143743031 |0 (DE-627)704589486 |0 (DE-576)338676589 |4 aut | |
| 700 | 1 | |8 1\p |a Sonntag, Johanna Sigrid Nelly |e VerfasserIn |0 (DE-588)1037890205 |0 (DE-627)75640925X |0 (DE-576)391932977 |4 aut | |
| 700 | 1 | |a Tarade, Nooraldeen |d 1991- |e VerfasserIn |0 (DE-588)1262487838 |0 (DE-627)1810176964 |4 aut | |
| 700 | 1 | |a Bernhardt, Stephan |e VerfasserIn |0 (DE-588)1147341044 |0 (DE-627)1006090363 |0 (DE-576)495806331 |4 aut | |
| 700 | 1 | |8 2\p |a Fehling-Kaschek, Mirjam |e VerfasserIn |0 (DE-588)1059249871 |0 (DE-627)798196947 |0 (DE-576)399677704 |4 aut | |
| 700 | 1 | |a Hasmann, Max |e VerfasserIn |4 aut | |
| 700 | 1 | |8 3\p |a Korf, Ulrike |d 1963- |e VerfasserIn |0 (DE-588)172660920 |0 (DE-627)697594440 |0 (DE-576)133519465 |4 aut | |
| 700 | 1 | |a Wiemann, Stefan |e VerfasserIn |0 (DE-588)1105581209 |0 (DE-627)862699134 |0 (DE-576)473627191 |4 aut | |
| 700 | 1 | |8 4\p |a Timmer, Jens |d 1964- |e VerfasserIn |0 (DE-588)114318549 |0 (DE-627)562988742 |0 (DE-576)289793092 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cancers |d Basel : MDPI, 2009 |g 14(2022), 10, Artikel-ID 2379, Seite 1-24 |h Online-Ressource |w (DE-627)614095670 |w (DE-600)2527080-1 |w (DE-576)313958548 |x 2072-6694 |7 nnas |a Disentangling ERBB signaling in breast cancer subtypes a model-based Analysis |
| 773 | 1 | 8 | |g volume:14 |g year:2022 |g number:10 |g elocationid:2379 |g pages:1-24 |g extent:24 |a Disentangling ERBB signaling in breast cancer subtypes a model-based Analysis |
| 856 | 4 | 0 | |u https://doi.org/10.3390/cancers14102379 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.mdpi.com/2072-6694/14/10/2379 |x Verlag |z lizenzpflichtig |3 Volltext |
| 883 | |8 1\p |a cgwrk |d 20241001 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | ||
| 883 | |8 2\p |a cgwrk |d 20241001 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | ||
| 883 | |8 3\p |a cgwrk |d 20241001 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | ||
| 883 | |8 4\p |a cgwrk |d 20241001 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | ||
| 951 | |a AR | ||
| 992 | |a 20220714 | ||
| 993 | |a Article | ||
| 994 | |a 2022 | ||
| 998 | |g 1105581209 |a Wiemann, Stefan |m 1105581209:Wiemann, Stefan |d 140000 |e 140000PW1105581209 |k 0/140000/ |p 6 | ||
| 998 | |g 1147341044 |a Bernhardt, Stephan |m 1147341044:Bernhardt, Stephan |p 6 | ||
| 998 | |g 1262487838 |a Tarade, Nooraldeen |m 1262487838:Tarade, Nooraldeen |d 140000 |e 140000PT1262487838 |k 0/140000/ |p 5 | ||
| 998 | |g 143743031 |a Reinz, Eileen |m 143743031:Reinz, Eileen |d 140000 |e 140000PR143743031 |k 0/140000/ |p 3 | ||
| 999 | |a KXP-PPN1810175704 |e 4165531316 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"language":["eng"],"physDesc":[{"extent":"24 S."}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"person":[{"family":"Kemmer","role":"aut","given":"Svenja","display":"Kemmer, Svenja"},{"display":"Berdiel-Acer, Mireia","given":"Mireia","role":"aut","family":"Berdiel-Acer"},{"role":"aut","given":"Eileen","family":"Reinz","display":"Reinz, Eileen"},{"family":"Sonntag","role":"aut","given":"Johanna Sigrid Nelly","display":"Sonntag, Johanna Sigrid Nelly"},{"display":"Tarade, Nooraldeen","given":"Nooraldeen","role":"aut","family":"Tarade"},{"display":"Bernhardt, Stephan","family":"Bernhardt","given":"Stephan","role":"aut"},{"display":"Fehling-Kaschek, Mirjam","family":"Fehling-Kaschek","given":"Mirjam","role":"aut"},{"given":"Max","role":"aut","family":"Hasmann","display":"Hasmann, Max"},{"display":"Korf, Ulrike","role":"aut","given":"Ulrike","family":"Korf"},{"given":"Stefan","role":"aut","family":"Wiemann","display":"Wiemann, Stefan"},{"given":"Jens","role":"aut","family":"Timmer","display":"Timmer, Jens"}],"title":[{"title":"Disentangling ERBB signaling in breast cancer subtypes","subtitle":"a model-based Analysis","title_sort":"Disentangling ERBB signaling in breast cancer subtypes"}],"name":{"displayForm":["Svenja Kemmer, Mireia Berdiel-Acer, Eileen Reinz, Johanna Sonntag, Nooraldeen Tarade, Stephan Bernhardt, Mirjam Fehling-Kaschek, Max Hasmann, Ulrike Korf, Stefan Wiemann and Jens Timmer"]},"recId":"1810175704","id":{"eki":["1810175704"],"doi":["10.3390/cancers14102379"]},"origin":[{"dateIssuedDisp":"12 May 2022","dateIssuedKey":"2022"}],"note":["Gesehen am 14.07.2022"],"relHost":[{"physDesc":[{"extent":"Online-Ressource"}],"pubHistory":["1.2009 -"],"language":["eng"],"note":["Gesehen am 27.05.2020"],"type":{"bibl":"periodical","media":"Online-Ressource"},"title":[{"title_sort":"Cancers","title":"Cancers"}],"disp":"Disentangling ERBB signaling in breast cancer subtypes a model-based AnalysisCancers","recId":"614095670","name":{"displayForm":["Molecular Diversity Preservation International (MDPI)"]},"part":{"year":"2022","issue":"10","extent":"24","text":"14(2022), 10, Artikel-ID 2379, Seite 1-24","pages":"1-24","volume":"14"},"origin":[{"dateIssuedKey":"2009","publisher":"MDPI","dateIssuedDisp":"2009-","publisherPlace":"Basel"}],"id":{"eki":["614095670"],"zdb":["2527080-1"],"issn":["2072-6694"]}}]} | ||
| SRT | |a KEMMERSVENDISENTANGL1220 | ||