LIVIVO - Search results -

Search results

Result 1 - 10 of total 11

Search options

Article ; Online: Biomarker Testing Journey Among Patients with Advanced Solid Tumors and Treatment Patterns by Homologous Recombination Repair Status: A Clinico-Genomic Database Study.

Shao, Changxia / Ren, Yixin / Zhou, Heng / Lee, Liam C / Chen, Cai / Dettman, Elisha J / Cristescu, Razvan / Gozman, Alexander / Jin, Fan / Zhou, Wei

Advances in therapy

2024 Volume 41, Issue 2, Page(s) 759–776

Abstract: Introduction: Defects in the homologous recombination repair (HRR) pathway can include mutations in BRCA1 and BRCA2 (BRCAm) and other HRR genes (HRRm). These mutations are associated with a homologous recombination deficiency (HRD) phenotype. We ... ...

Abstract	Introduction: Defects in the homologous recombination repair (HRR) pathway can include mutations in BRCA1 and BRCA2 (BRCAm) and other HRR genes (HRRm). These mutations are associated with a homologous recombination deficiency (HRD) phenotype. We evaluated testing journey and treatment patterns by BRCAm, HRRm, and HRD status in a real-world dataset. Methods: Deidentified data for patients who had undergone comprehensive genomic profiling using FoundationOne Results: Among 9457 patients included in the overall population with evaluable biomarker status, 7856 (83.1%) received ≥ 1 systemic therapy. Among the 7856 patients who received systemic therapy, 2324 (30.0%) underwent testing before first-line therapy, 4114 (52.4%) were tested after receiving first-line therapy and before receiving subsequent therapy (if any), 970 (12.3%) were tested after second-line therapy and before receiving subsequent therapy (if any), and 447 (5.7%) patients underwent testing after receiving third-line therapy. A higher proportion of patients with BRCAm, HRRm, or HRD-positive status were treated with poly(ADP-ribose) polymerase (PARP) inhibitors across all lines of therapy. There was no evidence of a meaningful difference in the proportion of patients who received other treatment (including chemotherapy and immunotherapy) by BRCAm, HRRm, or HRD status. Conclusion: The majority of patients from this real-world dataset underwent FoundationOne
MeSH term(s)	Humans ; Female ; Recombinational DNA Repair ; Neoplasms/drug therapy ; Neoplasms/genetics ; Mutation ; Biomarkers ; Genomics ; Ovarian Neoplasms/pathology
Chemical Substances	Biomarkers
Language	English
Publishing date	2024-01-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	632651-1
ISSN	1865-8652 ; 0741-238X
ISSN (online)	1865-8652
ISSN	0741-238X
DOI	10.1007/s12325-023-02734-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2101: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Association Between Homologous Recombination Repair Biomarkers and Survival in Patients With Solid Tumors.

Shao, Changxia / Ren, Yixin / Zhou, Heng / Chen, Cai / Dettman, Elisha J / Lee, Liam C / Cristescu, Razvan / Gozman, Alexander / Jin, Fan / Zhou, Wei

JCO precision oncology

2023 Volume 7, Page(s) e2300195

Abstract: Purpose: Mutations in : Methods: Deidentified data were collected through December 31, 2020, from a real-world clinicogenomic database (CGDB) with data originating from approximately 280 cancer clinics in the United States. Patients age 18 years and ... ...

Abstract	Purpose: Mutations in Methods: Deidentified data were collected through December 31, 2020, from a real-world clinicogenomic database (CGDB) with data originating from approximately 280 cancer clinics in the United States. Patients age 18 years and older with an advanced/metastatic diagnosis between 2018 and 2019 for 1 of 15 solid tumors and available data in the CGDB were included. The primary analysis evaluated the association between HRR pathway biomarkers and OS, using start of second-line therapy as the index date (to reduce immortal time bias). Results: A total of 9,457 patients had available data for BRCA/HRR and 5,792 for HRD status; 4,890 (51.7%) were women and mean (SD) age was 65.9 (11.5) years. For the primary analysis, adjusted hazard ratios for OS were BRCAm (n = 156) versus BRCA wild-type (wt; n = 3,131; 0.83 [95% CI, 0.60 to 1.17]); for HRRm (n = 467) versus HRRwt (n = 282; 0.95 [95% CI, 0.79 to 1.14]); and for HRD-positive (n = 447) versus -negative (n = 1,687; 1.22 [95% CI, 1.02 to 1.47]). Results were similar using start of first-line and start of third-line therapy as index dates. Conclusion: This large, real-world study found no association between OS and either BRCA or HRR status but identified a possible linkage between HRD positivity and shorter median OS in patients with advanced solid tumors who did not receive PARPi or immunotherapy.
MeSH term(s)	Humans ; Female ; Adolescent ; Aged ; Male ; Recombinational DNA Repair/genetics ; Neoplasms/genetics ; Neoplasms/therapy ; DNA Repair ; Poly(ADP-ribose) Polymerase Inhibitors ; Biomarkers, Tumor/genetics
Chemical Substances	Poly(ADP-ribose) Polymerase Inhibitors ; Biomarkers, Tumor
Language	English
Publishing date	2023-11-15
Publishing country	United States
Document type	Journal Article
ISSN	2473-4284
ISSN (online)	2473-4284
DOI	10.1200/PO.23.00195
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Targeting NRAS via miR-1304-5p or farnesyltransferase inhibition confers sensitivity to ALK inhibitors in ALK-mutant neuroblastoma.

Nature communications

2024 Volume 15, Issue 1, Page(s) 3422

Abstract: Targeting Anaplastic lymphoma kinase (ALK) is a promising therapeutic strategy for aberrant ALK-expressing malignancies including neuroblastoma, but resistance to ALK tyrosine kinase inhibitors (ALK TKI) is a distinct possibility necessitating drug ... ...

Abstract	Targeting Anaplastic lymphoma kinase (ALK) is a promising therapeutic strategy for aberrant ALK-expressing malignancies including neuroblastoma, but resistance to ALK tyrosine kinase inhibitors (ALK TKI) is a distinct possibility necessitating drug combination therapeutic approaches. Using high-throughput, genome-wide CRISPR-Cas9 knockout screens, we identify miR-1304-5p loss as a desensitizer to ALK TKIs in aberrant ALK-expressing neuroblastoma; inhibition of miR-1304-5p decreases, while mimics of this miRNA increase the sensitivity of neuroblastoma cells to ALK TKIs. We show that miR-1304-5p targets NRAS, decreasing cell viability via induction of apoptosis. It follows that the farnesyltransferase inhibitor (FTI) lonafarnib in addition to ALK TKIs act synergistically in neuroblastoma, inducing apoptosis in vitro. In particular, on combined treatment of neuroblastoma patient derived xenografts with an FTI and an ALK TKI complete regression of tumour growth is observed although tumours rapidly regrow on cessation of therapy. Overall, our data suggests that combined use of ALK TKIs and FTIs, constitutes a therapeutic approach to treat high risk neuroblastoma although prolonged therapy is likely required to prevent relapse.
MeSH term(s)	Animals ; Female ; Humans ; Mice ; Anaplastic Lymphoma Kinase/genetics ; Anaplastic Lymphoma Kinase/metabolism ; Anaplastic Lymphoma Kinase/antagonists & inhibitors ; Apoptosis/drug effects ; Apoptosis/genetics ; Cell Line, Tumor ; Dibenzocycloheptenes ; Drug Resistance, Neoplasm/genetics ; Drug Resistance, Neoplasm/drug effects ; Drug Synergism ; Farnesyltranstransferase/antagonists & inhibitors ; Farnesyltranstransferase/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; GTP Phosphohydrolases/genetics ; GTP Phosphohydrolases/metabolism ; Membrane Proteins/metabolism ; Membrane Proteins/genetics ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Mutation ; Neuroblastoma/drug therapy ; Neuroblastoma/genetics ; Neuroblastoma/pathology ; Neuroblastoma/metabolism ; Piperidines/pharmacology ; Piperidines/therapeutic use ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Pyridines/pharmacology ; Pyridines/therapeutic use ; Xenograft Model Antitumor Assays
Chemical Substances	ALK protein, human (EC 2.7.10.1) ; Anaplastic Lymphoma Kinase (EC 2.7.10.1) ; Dibenzocycloheptenes ; Farnesyltranstransferase (EC 2.5.1.29) ; GTP Phosphohydrolases (EC 3.6.1.-) ; lonafarnib (IOW153004F) ; Membrane Proteins ; MicroRNAs ; NRAS protein, human (EC 3.6.1.-) ; Piperidines ; Protein Kinase Inhibitors ; Pyridines
Language	English
Publishing date	2024-04-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-47771-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: MAP kinase and autophagy pathways cooperate to maintain RAS mutant cancer cell survival.

Lee, Chih-Shia / Lee, Liam C / Yuan, Tina L / Chakka, Sirisha / Fellmann, Christof / Lowe, Scott W / Caplen, Natasha J / McCormick, Frank / Luo, Ji

Proceedings of the National Academy of Sciences of the United States of America

2019 Volume 116, Issue 10, Page(s) 4508–4517

Abstract: Oncogenic mutations in the small GTPase KRAS are frequently found in human cancers, and, currently, there are no effective targeted therapies for these tumors. Using a combinatorial siRNA approach, we analyzed a panel ... ...

Abstract	Oncogenic mutations in the small GTPase KRAS are frequently found in human cancers, and, currently, there are no effective targeted therapies for these tumors. Using a combinatorial siRNA approach, we analyzed a panel of
MeSH term(s)	Autophagic Cell Death ; Caco-2 Cells ; Cell Survival/genetics ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Extracellular Signal-Regulated MAP Kinases/genetics ; Extracellular Signal-Regulated MAP Kinases/metabolism ; HCT116 Cells ; Humans ; MAP Kinase Signaling System ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/metabolism ; Proto-Oncogene Proteins p21(ras)/genetics ; Proto-Oncogene Proteins p21(ras)/metabolism
Chemical Substances	KRAS protein, human ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
Language	English
Publishing date	2019-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1817494116
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1148: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Paediatric Burkitt lymphoma patient-derived xenografts capture disease characteristics over time and are a model for therapy.

Forde, Sorcha / Matthews, Jamie D / Jahangiri, Leila / Lee, Liam C / Prokoph, Nina / Malcolm, Tim I M / Giger, Olivier T / Bell, Natalie / Blair, Helen / O'Marcaigh, Aengus / Smith, Owen / Kenner, Lukas / Bomken, Simon / Burke, Gladstone A A / Turner, Suzanne D

British journal of haematology

2020 Volume 192, Issue 2, Page(s) 354–365

Abstract: Burkitt lymphoma (BL) accounts for almost two-thirds of all B-cell non-Hodgkin lymphoma (B-NHL) in children and adolescents and is characterised by a MYC translocation and rapid cell turnover. Intensive chemotherapeutic regimens have been developed in ... ...

Abstract	Burkitt lymphoma (BL) accounts for almost two-thirds of all B-cell non-Hodgkin lymphoma (B-NHL) in children and adolescents and is characterised by a MYC translocation and rapid cell turnover. Intensive chemotherapeutic regimens have been developed in recent decades, including the lymphomes malins B (LMB) protocol, which have resulted in a survival rate in excess of 90%. Recent clinical trials have focused on immunochemotherapy, with the addition of rituximab to chemotherapeutic backbones, showing encouraging results. Despite these advances, relapse and refractory disease occurs in up to 10% of patients and salvage options for these carry a dismal prognosis. Efforts to better understand the molecular and functional characteristics driving relapse and refractory disease may help improve this prognosis. This study has established a paediatric BL patient-derived xenograft (PDX) resource which captures and maintains tumour heterogeneity, may be used to better characterise tumours and identify cell populations responsible for therapy resistance.
MeSH term(s)	Animals ; Burkitt Lymphoma/genetics ; Burkitt Lymphoma/pathology ; Burkitt Lymphoma/therapy ; Child ; Disease Models, Animal ; Female ; Gene Expression Regulation, Neoplastic ; Heterografts/pathology ; Humans ; Male ; Mice ; Neoplasm Transplantation ; Tumor Cells, Cultured
Language	English
Publishing date	2020-09-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.17043
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Uh III Zs.182: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: One-step immortalization of primary human airway epithelial cells capable of oncogenic transformation.

Smith, Jordan L / Lee, Liam C / Read, Abigail / Li, Qiuning / Yu, Bing / Lee, Chih-Shia / Luo, Ji

Cell & bioscience

2016 Volume 6, Page(s) 57

Abstract: Background: The ability to transform normal human cells into cancer cells with the introduction of defined genetic alterations is a valuable method for understanding the mechanisms of oncogenesis. Easy establishment of immortalized but non-transformed ... ...

Abstract	Background: The ability to transform normal human cells into cancer cells with the introduction of defined genetic alterations is a valuable method for understanding the mechanisms of oncogenesis. Easy establishment of immortalized but non-transformed human cells from various tissues would facilitate these genetic analyses. Results: We report here a simple, one-step immortalization method that involves retroviral vector mediated co-expression of the human telomerase protein and a shRNA targeting the Conclusions: Our method simplifies the immortalization process and is broadly applicable for establishing immortalized epithelial cell lines from primary human tissues for cancer research.
Language	English
Publishing date	2016-11-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2593367-X
ISSN	2045-3701
ISSN	2045-3701
DOI	10.1186/s13578-016-0122-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status.

Nature communications

2019 Volume 10, Issue 1, Page(s) 5428

Abstract: Resistance to anaplastic lymphoma kinase (ALK)-targeted therapy in ALK-positive non-small cell lung cancer has been reported, with the majority of acquired resistance mechanisms relying on bypass signaling. To proactively identify resistance mechanisms ... ...

Abstract	Resistance to anaplastic lymphoma kinase (ALK)-targeted therapy in ALK-positive non-small cell lung cancer has been reported, with the majority of acquired resistance mechanisms relying on bypass signaling. To proactively identify resistance mechanisms in ALK-positive neuroblastoma (NB), we herein employ genome-wide CRISPR activation screens of NB cell lines treated with brigatinib or ceritinib, identifying PIM1 as a putative resistance gene, whose high expression is associated with high-risk disease and poor survival. Knockdown of PIM1 sensitizes cells of differing MYCN status to ALK inhibitors, and in patient-derived xenografts of high-risk NB harboring ALK mutations, the combination of the ALK inhibitor ceritinib and PIM1 inhibitor AZD1208 shows significantly enhanced anti-tumor efficacy relative to single agents. These data confirm that PIM1 overexpression decreases sensitivity to ALK inhibitors in NB, and suggests that combined front-line inhibition of ALK and PIM1 is a viable strategy for the treatment of ALK-positive NB independent of MYCN status.
MeSH term(s)	Anaplastic Lymphoma Kinase/antagonists & inhibitors ; Anaplastic Lymphoma Kinase/genetics ; Animals ; Apoptosis/drug effects ; Biphenyl Compounds/pharmacology ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics ; Gene Knockdown Techniques ; Humans ; Mice ; N-Myc Proto-Oncogene Protein/genetics ; Neuroblastoma/drug therapy ; Neuroblastoma/genetics ; Organophosphorus Compounds/therapeutic use ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins c-pim-1/antagonists & inhibitors ; Proto-Oncogene Proteins c-pim-1/genetics ; Pyrimidines/pharmacology ; Pyrimidines/therapeutic use ; Sulfones/pharmacology ; Sulfones/therapeutic use ; Thiazolidines/pharmacology ; Xenograft Model Antitumor Assays
Chemical Substances	AZD1208 ; Biphenyl Compounds ; MYCN protein, human ; N-Myc Proto-Oncogene Protein ; Organophosphorus Compounds ; Protein Kinase Inhibitors ; Pyrimidines ; Sulfones ; Thiazolidines ; ALK protein, human (EC 2.7.10.1) ; Anaplastic Lymphoma Kinase (EC 2.7.10.1) ; PIM1 protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins c-pim-1 (EC 2.7.11.1) ; brigatinib (HYW8DB273J) ; ceritinib (K418KG2GET)
Language	English
Publishing date	2019-11-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-019-13315-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Development of siRNA payloads to target KRAS-mutant cancer.

Yuan, Tina L / Fellmann, Christof / Lee, Chih-Shia / Ritchie, Cayde D / Thapar, Vishal / Lee, Liam C / Hsu, Dennis J / Grace, Danielle / Carver, Joseph O / Zuber, Johannes / Luo, Ji / McCormick, Frank / Lowe, Scott W

Cancer discovery

2014 Volume 4, Issue 10, Page(s) 1182–1197

Abstract: Unlabelled: RNAi is a powerful tool for target identification and can lead to novel therapies for pharmacologically intractable targets such as KRAS. RNAi therapy must combine potent siRNA payloads with reliable in vivo delivery for efficient target ... ...

Abstract	Unlabelled: RNAi is a powerful tool for target identification and can lead to novel therapies for pharmacologically intractable targets such as KRAS. RNAi therapy must combine potent siRNA payloads with reliable in vivo delivery for efficient target inhibition. We used a functional "Sensor" assay to establish a library of potent siRNAs against RAS pathway genes and to show that they efficiently suppress their targets at low dose. This reduces off-target effects and enables combination gene knockdown. We administered Sensor siRNAs in vitro and in vivo and validated the delivery of KRAS siRNA alone and siRNA targeting the complete RAF effector node (A/B/CRAF) as promising strategies to treat KRAS-mutant colorectal cancer. We further demonstrate that improved therapeutic efficacy is achieved by formulating siRNA payloads that combine both single-gene siRNA and node-targeted siRNAs (KRAS + PIK3CA/B). The customizable nature of Sensor siRNA payloads offers a universal platform for the combination target identification and development of RNAi therapeutics. Significance: To advance RNAi therapy for KRAS-mutant cancer, we developed a validated siRNA library against RAS pathway genes that enables combination gene silencing. Using an in vivo model for real-time siRNA delivery tracking, we show that siRNA-mediated inhibition of KRAS as well as RAF or PI3K combinations can impair KRAS-mutant colorectal cancer in xenograft models.
MeSH term(s)	Animals ; Cell Line, Tumor ; Cluster Analysis ; Disease Models, Animal ; Drug Delivery Systems ; Gene Expression Profiling ; Gene Knockdown Techniques ; Gene Library ; Gene Transfer Techniques ; Genes, ras ; Humans ; Mice ; Mutation ; Nanoparticles ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; RNA Interference ; RNA, Small Interfering/administration & dosage ; RNA, Small Interfering/genetics ; Reproducibility of Results ; Signal Transduction ; Tumor Burden/genetics ; Xenograft Model Antitumor Assays
Chemical Substances	RNA, Small Interfering ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-)
Language	English
Publishing date	2014-08-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2625242-9
ISSN	2159-8290 ; 2159-8274
ISSN (online)	2159-8290
ISSN	2159-8274
DOI	10.1158/2159-8290.CD-13-0900
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6916: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Oncogenesis driven by the Ras/Raf pathway requires the SUMO E2 ligase Ubc9.

Yu, Bing / Swatkoski, Stephen / Holly, Alesia / Lee, Liam C / Giroux, Valentin / Lee, Chih-Shia / Hsu, Dennis / Smith, Jordan L / Yuen, Garmen / Yue, Junqiu / Ann, David K / Simpson, R Mark / Creighton, Chad J / Figg, William D / Gucek, Marjan / Luo, Ji

Proceedings of the National Academy of Sciences of the United States of America

2015 Volume 112, Issue 14, Page(s) E1724–33

Abstract: The small GTPase KRAS is frequently mutated in human cancer and currently there are no targeted therapies for KRAS mutant tumors. Here, we show that the small ubiquitin-like modifier (SUMO) pathway is required for KRAS-driven transformation. RNAi ... ...

Abstract	The small GTPase KRAS is frequently mutated in human cancer and currently there are no targeted therapies for KRAS mutant tumors. Here, we show that the small ubiquitin-like modifier (SUMO) pathway is required for KRAS-driven transformation. RNAi depletion of the SUMO E2 ligase Ubc9 suppresses 3D growth of KRAS mutant colorectal cancer cells in vitro and attenuates tumor growth in vivo. In KRAS mutant cells, a subset of proteins exhibit elevated levels of SUMOylation. Among these proteins, KAP1, CHD1, and EIF3L collectively support anchorage-independent growth, and the SUMOylation of KAP1 is necessary for its activity in this context. Thus, the SUMO pathway critically contributes to the transformed phenotype of KRAS mutant cells and Ubc9 presents a potential target for the treatment of KRAS mutant colorectal cancer.
MeSH term(s)	Animals ; Caco-2 Cells ; Carcinogenesis ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Gene Expression Regulation, Neoplastic ; Genes, ras ; HCT116 Cells ; Humans ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Mutation ; Neoplasm Transplantation ; RNA Interference ; RNA, Small Interfering/metabolism ; Ubiquitin-Conjugating Enzymes/metabolism ; raf Kinases/metabolism ; ras Proteins/metabolism
Chemical Substances	RNA, Small Interfering ; Ubiquitin-Conjugating Enzymes (EC 2.3.2.23) ; raf Kinases (EC 2.7.11.1) ; ras Proteins (EC 3.6.5.2) ; ubiquitin-conjugating enzyme UBC9 (EC 6.3.2.-)
Language	English
Publishing date	2015-03-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1415569112
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1148: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: CRIPTO1 expression in EGFR-mutant NSCLC elicits intrinsic EGFR-inhibitor resistance.

Park, Kang-Seo / Raffeld, Mark / Moon, Yong Wha / Xi, Liqiang / Bianco, Caterina / Pham, Trung / Lee, Liam C / Mitsudomi, Tetsuya / Yatabe, Yasushi / Okamoto, Isamu / Subramaniam, Deepa / Mok, Tony / Rosell, Rafael / Luo, Ji / Salomon, David S / Wang, Yisong / Giaccone, Giuseppe

The Journal of clinical investigation

2014 Volume 124, Issue 7, Page(s) 3003–3015

Abstract: The majority of non-small cell lung cancer (NSCLC) patients harbor EGFR-activating mutations that can be therapeutically targeted by EGFR tyrosine kinase inhibitors (EGFR-TKI), such as erlotinib and gefitinib. Unfortunately, a subset of patients with ... ...

Abstract	The majority of non-small cell lung cancer (NSCLC) patients harbor EGFR-activating mutations that can be therapeutically targeted by EGFR tyrosine kinase inhibitors (EGFR-TKI), such as erlotinib and gefitinib. Unfortunately, a subset of patients with EGFR mutations are refractory to EGFR-TKIs. Resistance to EGFR inhibitors reportedly involves SRC activation and induction of epithelial-to-mesenchymal transition (EMT). Here, we have demonstrated that overexpression of CRIPTO1, an EGF-CFC protein family member, renders EGFR-TKI-sensitive and EGFR-mutated NSCLC cells resistant to erlotinib in culture and in murine xenograft models. Furthermore, tumors from NSCLC patients with EGFR-activating mutations that were intrinsically resistant to EGFR-TKIs expressed higher levels of CRIPTO1 compared with tumors from patients that were sensitive to EGFR-TKIs. Primary NSCLC cells derived from a patient with EGFR-mutated NSCLC that was intrinsically erlotinib resistant were CRIPTO1 positive, but gained erlotinib sensitivity upon loss of CRIPTO1 expression during culture. CRIPTO1 activated SRC and ZEB1 to promote EMT via microRNA-205 (miR-205) downregulation. While miR-205 depletion induced erlotinib resistance, miR-205 overexpression inhibited CRIPTO1-dependent ZEB1 and SRC activation, restoring erlotinib sensitivity. CRIPTO1-induced erlotinib resistance was directly mediated through SRC but not ZEB1; therefore, cotargeting EGFR and SRC synergistically attenuated growth of erlotinib-resistant, CRIPTO1-positive, EGFR-mutated NSCLC cells in vitro and in vivo, suggesting that this combination may overcome intrinsic EGFR-inhibitor resistance in patients with CRIPTO1-positive, EGFR-mutated NSCLC.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/metabolism ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics ; Epithelial-Mesenchymal Transition ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/genetics ; Erlotinib Hydrochloride ; GPI-Linked Proteins/genetics ; GPI-Linked Proteins/metabolism ; Gefitinib ; Genes, erbB-1 ; Homeodomain Proteins/metabolism ; Humans ; Intercellular Signaling Peptides and Proteins/genetics ; Intercellular Signaling Peptides and Proteins/metabolism ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Mice ; Mice, Nude ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Mutation ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Protein Kinase Inhibitors/pharmacology ; Quinazolines/pharmacology ; Transcription Factors/metabolism ; Xenograft Model Antitumor Assays ; Zinc Finger E-box-Binding Homeobox 1 ; src-Family Kinases/metabolism
Chemical Substances	Antineoplastic Agents ; GPI-Linked Proteins ; Homeodomain Proteins ; Intercellular Signaling Peptides and Proteins ; MIRN205 microRNA, human ; MicroRNAs ; Neoplasm Proteins ; Protein Kinase Inhibitors ; Quinazolines ; TDGF1 protein, human ; Transcription Factors ; ZEB1 protein, human ; Zinc Finger E-box-Binding Homeobox 1 ; Erlotinib Hydrochloride (DA87705X9K) ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; src-Family Kinases (EC 2.7.10.2) ; Gefitinib (S65743JHBS)
Language	English
Publishing date	2014-06-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI73048
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ua VI Zs.184: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito