| |  Online-Ressource |
|---|
| Verfasst von: | Díaz-Jiménez, Alberto [VerfasserIn]  |
|---|
| | Ramos, Maria [VerfasserIn] |
|---|
| | Helm, Barbara [VerfasserIn] |
|---|
| | Chocarro, Sara [VerfasserIn] |
|---|
| | Frey, Dario [VerfasserIn] |
|---|
| | Agrawal, Shubham [VerfasserIn] |
|---|
| | Somogyi, Kálmán [VerfasserIn] |
|---|
| | Klingmüller, Ursula [VerfasserIn] |
|---|
| | Lu, Junyan [VerfasserIn] |
|---|
| | Sotillo, Rocio [VerfasserIn] |
|---|
| Titel: | Concurrent inhibition of ALK and SRC kinases disrupts the ALK lung tumor cell proteome |
|---|
| Verf.angabe: | Alberto Diaz-Jimenez, Maria Ramos, Barbara Helm, Sara Chocarro, Dario Lucas Frey, Shubham Agrawal, Kalman Somogyi, Ursula Klingmüller, Junyan Lu, Rocio Sotillo |
|---|
| E-Jahr: | 2024 |
|---|
| Jahr: | 19 March 2024 |
|---|
| Umfang: | 18 S. |
|---|
| Fussnoten: | Gesehen am 18.10.2024 |
|---|
| Titel Quelle: | Enthalten in: Drug resistance updates |
|---|
| Ort Quelle: | Oxford : Elsevier, 1998 |
|---|
| Jahr Quelle: | 2024 |
|---|
| Band/Heft Quelle: | 74(2024), Artikel-ID 101081, Seite 101081-1-101081-18 |
|---|
| ISSN Quelle: | 1532-2084 |
|---|
| Abstract: | Precision oncology has revolutionized the treatment of ALK-positive lung cancer with targeted therapies. However, an unmet clinical need still to address is the treatment of refractory tumors that contain drug-induced resistant mutations in the driver oncogene or exhibit resistance through the activation of diverse mechanisms. In this study, we established mouse tumor-derived cell models representing the two most prevalent EML4-ALK variants in human lung adenocarcinomas and characterized their proteomic profiles to gain insights into the underlying resistance mechanisms. We showed that Eml4-Alk variant 3 confers a worse response to ALK inhibitors, suggesting its role in promoting resistance to targeted therapy. In addition, proteomic analysis of brigatinib-treated cells revealed the upregulation of SRC kinase, a protein frequently activated in cancer. Co-targeting of ALK and SRC showed remarkable inhibitory effects in both ALK-driven murine and ALK-patient-derived lung tumor cells. This combination induced cell death through a multifaceted mechanism characterized by profound perturbation of the (phospho)proteomic landscape and a synergistic suppressive effect on the mTOR pathway. Our study demonstrates that the simultaneous inhibition of ALK and SRC can potentially overcome resistance mechanisms and enhance clinical outcomes in ALK-positive lung cancer patients. - One Sentence Summary - Co-targeting ALK and SRC enhances ALK inhibitor response in lung cancer by affecting the proteomic profile, offering hope for overcoming resistance and improving clinical outcomes. |
|---|
| DOI: | doi:10.1016/j.drup.2024.101081 |
|---|
| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.drup.2024.101081 |
|---|
| | Volltext: https://www.sciencedirect.com/science/article/pii/S1368764624000396 |
|---|
| | DOI: https://doi.org/10.1016/j.drup.2024.101081 |
|---|
| Datenträger: | Online-Ressource |
|---|
| Sprache: | eng |
|---|
| Sach-SW: | ALK |
|---|
| | Lung Cancer |
|---|
| | Resistance |
|---|
| | SRC |
|---|
| | Targeted therapy |
|---|
| K10plus-PPN: | 1906018103 |
|---|
| Verknüpfungen: | → Zeitschrift |
|---|
Concurrent inhibition of ALK and SRC kinases disrupts the ALK lung tumor cell proteome / Díaz-Jiménez, Alberto [VerfasserIn]; 19 March 2024 (Online-Ressource)
