5 results on '"Olivas V"'
Search Results
2. Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer.
- Author
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Haderk F, Chou YT, Cech L, Fernández-Méndez C, Yu J, Olivas V, Meraz IM, Barbosa Rabago D, Kerr DL, Gomez C, Allegakoen DV, Guan J, Shah KN, Herrington KA, Gbenedio OM, Nanjo S, Majidi M, Tamaki W, Pourmoghadam YK, Rotow JK, McCoach CE, Riess JW, Gutkind JS, Tang TT, Post L, Huang B, Santisteban P, Goodarzi H, Bandyopadhyay S, Kuo CJ, Roose JP, Wu W, Blakely CM, Roth JA, and Bivona TG
- Subjects
- Humans, Cell Line, Tumor, Animals, Adaptor Proteins, Signal Transducing metabolism, Adaptor Proteins, Signal Transducing genetics, Neoplasm, Residual, Mice, Focal Adhesion Kinase 1 metabolism, Focal Adhesion Kinase 1 genetics, ErbB Receptors metabolism, ErbB Receptors genetics, Anaplastic Lymphoma Kinase metabolism, Anaplastic Lymphoma Kinase genetics, Anaplastic Lymphoma Kinase antagonists & inhibitors, Proto-Oncogene Proteins p21(ras) genetics, Proto-Oncogene Proteins p21(ras) metabolism, Focal Adhesion Protein-Tyrosine Kinases metabolism, Antineoplastic Agents therapeutic use, Antineoplastic Agents pharmacology, Xenograft Model Antitumor Assays, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms metabolism, Signal Transduction drug effects, Transcription Factors metabolism, Transcription Factors genetics, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Non-Small-Cell Lung pathology, YAP-Signaling Proteins metabolism, Drug Resistance, Neoplasm genetics
- Abstract
Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell lung cancer (NSCLC) subtypes with oncogenic alterations in EGFR, ALK and KRAS. The success of targeted therapy is limited by drug-tolerant persister cells (DTPs) which withstand and adapt to treatment and comprise the residual disease state that is typical during treatment with clinical targeted therapies. Here, we integrate studies in patient-derived and immunocompetent lung cancer models and clinical specimens obtained from patients on targeted therapy to uncover a focal adhesion kinase (FAK)-YAP signaling axis that promotes residual disease during oncogenic EGFR-, ALK-, and KRAS-targeted therapies. FAK-YAP signaling inhibition combined with the primary targeted therapy suppressed residual drug-tolerant cells and enhanced tumor responses. This study unveils a FAK-YAP signaling module that promotes residual disease in lung cancer and mechanism-based therapeutic strategies to improve tumor response., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
3. The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance.
- Author
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Caswell DR, Gui P, Mayekar MK, Law EK, Pich O, Bailey C, Boumelha J, Kerr DL, Blakely CM, Manabe T, Martinez-Ruiz C, Bakker B, De Dios Palomino Villcas J, I Vokes N, Dietzen M, Angelova M, Gini B, Tamaki W, Allegakoen P, Wu W, Humpton TJ, Hill W, Tomaschko M, Lu WT, Haderk F, Al Bakir M, Nagano A, Gimeno-Valiente F, de Carné Trécesson S, Vendramin R, Barbè V, Mugabo M, Weeden CE, Rowan A, McCoach CE, Almeida B, Green M, Gomez C, Nanjo S, Barbosa D, Moore C, Przewrocka J, Black JRM, Grönroos E, Suarez-Bonnet A, Priestnall SL, Zverev C, Lighterness S, Cormack J, Olivas V, Cech L, Andrews T, Rule B, Jiao Y, Zhang X, Ashford P, Durfee C, Venkatesan S, Temiz NA, Tan L, Larson LK, Argyris PP, Brown WL, Yu EA, Rotow JK, Guha U, Roper N, Yu J, Vogel RI, Thomas NJ, Marra A, Selenica P, Yu H, Bakhoum SF, Chew SK, Reis-Filho JS, Jamal-Hanjani M, Vousden KH, McGranahan N, Van Allen EM, Kanu N, Harris RS, Downward J, Bivona TG, and Swanton C
- Subjects
- Humans, Animals, Mice, Mutation, Up-Regulation genetics, ErbB Receptors genetics, ErbB Receptors metabolism, Cytidine Deaminase genetics, Minor Histocompatibility Antigens genetics, Minor Histocompatibility Antigens metabolism, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics
- Abstract
In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy., (© 2023. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
4. Author Correction: 3-Phosphoinositide-dependent kinase 1 drives acquired resistance to osimertinib.
- Author
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Meraz IM, Majidi M, Fang B, Meng F, Gao L, Shao R, Song R, Li F, Lissanu Y, Chen H, Ha MJ, Wang Q, Wang J, Shpall E, Jung SY, Haderk F, Gui P, Riess JW, Olivas V, Bivona TG, and Roth JA
- Published
- 2023
- Full Text
- View/download PDF
5. 3-Phosphoinositide-dependent kinase 1 drives acquired resistance to osimertinib.
- Author
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Meraz IM, Majidi M, Fang B, Meng F, Gao L, Shao R, Song R, Li F, Lissanu Y, Chen H, Ha MJ, Wang Q, Wang J, Shpall E, Jung SY, Haderk F, Gui P, Riess JW, Olivas V, Bivona TG, and Roth JA
- Subjects
- Mice, Animals, Humans, ErbB Receptors genetics, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt genetics, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Drug Resistance, Neoplasm genetics, Mutation, TOR Serine-Threonine Kinases genetics, Phosphatidylinositols, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology
- Abstract
Osimertinib sensitive and resistant NSCLC NCI-H1975 clones are used to model osimertinib acquired resistance in humanized and non-humanized mice and delineate potential resistance mechanisms. No new EGFR mutations or loss of the EGFR T790M mutation are found in resistant clones. Resistant tumors grown under continuous osimertinib pressure both in humanized and non-humanized mice show aggressive tumor regrowth which is significantly less sensitive to osimertinib as compared with parental tumors. 3-phosphoinositide-dependent kinase 1 (PDK1) is identified as a potential driver of osimertinib acquired resistance, and its selective inhibition by BX795 and CRISPR gene knock out, sensitizes resistant clones. In-vivo inhibition of PDK1 enhances the osimertinib sensitivity against osimertinib resistant xenograft and a patient derived xenograft (PDX) tumors. PDK1 knock-out dysregulates PI3K/Akt/mTOR signaling, promotes cell cycle arrest at the G1 phase. Yes-associated protein (YAP) and active-YAP are upregulated in resistant tumors, and PDK1 knock-out inhibits nuclear translocation of YAP. Higher expression of PDK1 and an association between PDK1 and YAP are found in patients with progressive disease following osimertinib treatment. PDK1 is a central upstream regulator of two critical drug resistance pathways: PI3K/AKT/mTOR and YAP., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
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