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Article ; Online: Emerging therapeutic strategies for enhancing sensitivity and countering resistance to programmed cell death protein 1 or programmed death-ligand 1 inhibitors in non-small cell lung cancer.

Villaruz, Liza C / Blumenschein, George R / Otterson, Gregory A / Leal, Ticiana A

2023 Volume 129, Issue 9, Page(s) 1319–1350

Abstract: The availability of agents targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint has transformed treatment of advanced and/or metastatic non-small cell lung cancer (NSCLC). However, a substantial ... ...

Abstract	The availability of agents targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint has transformed treatment of advanced and/or metastatic non-small cell lung cancer (NSCLC). However, a substantial proportion of patients treated with these agents do not respond or experience only a brief period of clinical benefit. Even among those whose disease responds, many subsequently experience disease progression. Consequently, novel approaches are needed that enhance antitumor immunity and counter resistance to PD-(L)1 inhibitors, thereby improving and/or prolonging responses and patient outcomes, in both PD-(L)1 inhibitor-sensitive and inhibitor-resistant NSCLC. Mechanisms contributing to sensitivity and/or resistance to PD-(L)1 inhibitors in NSCLC include upregulation of other immune checkpoints and/or the presence of an immunosuppressive tumor microenvironment, which represent potential targets for new therapies. This review explores novel therapeutic regimens under investigation for enhancing responses to PD-(L)1 inhibitors and countering resistance, and summarizes the latest clinical evidence in NSCLC.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/pathology ; Lung Neoplasms/pathology ; Immune Checkpoint Inhibitors/therapeutic use ; Programmed Cell Death 1 Receptor ; Immunotherapy/adverse effects ; B7-H1 Antigen ; Tumor Microenvironment
Chemical Substances	Immune Checkpoint Inhibitors ; Programmed Cell Death 1 Receptor ; B7-H1 Antigen
Language	English
Publishing date	2023-02-27
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.34683
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Article ; Online: Insulin-like growth factor receptor.

Blumenschein, George

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

2011 Volume 6, Issue 11 Suppl 4, Page(s) S1799–800

MeSH term(s)	Antineoplastic Agents/therapeutic use ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/metabolism ; Clinical Trials as Topic ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/metabolism ; Receptors, Somatomedin/antagonists & inhibitors ; Receptors, Somatomedin/metabolism
Chemical Substances	Antineoplastic Agents ; Receptors, Somatomedin
Language	English
Publishing date	2011-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2432037-7
ISSN	1556-1380 ; 1556-0864
ISSN (online)	1556-1380
ISSN	1556-0864
DOI	10.1097/01.JTO.0000407563.14653.0c
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Zs.A 6664: 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)
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Article ; Online: Sintilimab plus chemotherapy for first-line treatment of advanced or metastatic nonsquamous non-small-cell lung cancer: network meta-analysis.

Molife, Cliff / Brnabic, Alan / Stefaniak, Victoria J / Belger, Mark A / Gruver, Kristi / Chen, Jing V / Souri, Saman / Blumenschein, George R

Immunotherapy

2023 Volume 15, Issue 4, Page(s) 293–309

Abstract: Aim: ...

Abstract	Aim:
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/pathology ; Lung Neoplasms/pathology ; Pemetrexed/therapeutic use ; Platinum/therapeutic use ; Bayes Theorem ; Ipilimumab/therapeutic use ; Network Meta-Analysis ; Nivolumab/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Chemical Substances	sintilimab (8FU7FQ8UPK) ; Pemetrexed (04Q9AIZ7NO) ; Platinum (49DFR088MY) ; Ipilimumab ; Nivolumab (31YO63LBSN)
Language	English
Publishing date	2023-02-07
Publishing country	England
Document type	Systematic Review ; Meta-Analysis ; Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2495964-9
ISSN	1750-7448 ; 1750-743X
ISSN (online)	1750-7448
ISSN	1750-743X
DOI	10.2217/imt-2022-0252
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Article ; Online: Developmental antiangiogenic agents for the treatment of non-small cell lung cancer (NSCLC).

Blumenschein, George R

Investigational new drugs

2011 Volume 30, Issue 4, Page(s) 1802–1811

Abstract: Standard therapy for advanced or metastatic non-small cell lung cancer (NSCLC) has primarily consisted of traditional cytotoxic chemotherapy, although use of targeted therapies has been approved in specific settings. Antiangiogenic agents represent a ... ...

Abstract	Standard therapy for advanced or metastatic non-small cell lung cancer (NSCLC) has primarily consisted of traditional cytotoxic chemotherapy, although use of targeted therapies has been approved in specific settings. Antiangiogenic agents represent a promising therapeutic strategy for treatment of advanced NSCLC. Bevacizumab is currently approved when given in combination with first-line platinum-based therapy in selected patients with nonsquamous NSCLC. Bevacizumab may also provide benefit in other clinical settings, as a part of a combination or maintenance strategy. Other antiangiogenic agents under development, including multi-targeted kinase inhibitors (MTKIs) and antibody-based agents, have exhibited mixed results in the NSCLC population. Published efficacy and safety data from clinical trials for antiangiogenic agents are reviewed, with an emphasis on novel agents and novel settings for established agents. Identification of biomarkers associated with improved efficacy may help select patients likely to receive the most benefit from these agents and may improve outcomes through development of personalized therapeutic strategies.
MeSH term(s)	Angiogenesis Inhibitors/pharmacology ; Angiogenesis Inhibitors/therapeutic use ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Humans ; Lung Neoplasms/drug therapy ; Molecular Targeted Therapy ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A
Language	English
Publishing date	2011-10-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	604895-x
ISSN	1573-0646 ; 0167-6997
ISSN (online)	1573-0646
ISSN	0167-6997
DOI	10.1007/s10637-011-9750-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Sorafenib in lung cancer: clinical developments and future directions.

Blumenschein, George

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

2008 Volume 3, Issue 6 Suppl 2, Page(s) S124–7

Abstract: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States. Angiogenesis, primarily mediated through vascular endothelial growth factor (VEGF), is one of the key steps in tumor growth and metastasis. VEGF is now ... ...

Abstract	Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States. Angiogenesis, primarily mediated through vascular endothelial growth factor (VEGF), is one of the key steps in tumor growth and metastasis. VEGF is now a validated target for NSCLC based on the results of the Eastern Cooperative Oncology Group trial E4599 which showed that the addition of bevacizumab, a VEGF monoclonal antibody, to cytotoxic chemotherapy improves survival compared with chemotherapy alone in patients with metastatic NSCLC. As NSCLC has complex and integrated signaling pathways, a rational approach is to target more than one of these pathways concurrently. Sorafenib, which is approved for the treatment of renal cell carcinoma, is a multitargeted signal transduction inhibitor that inhibits raf-kinases, VEGF receptor-2, platelet derived growth factor receptor-B, and c-kit. In a phase II monotherapy trial in patients with previously treated NSCLC, sorafenib demonstrated activity with a disease control rate and survival rate comparable to other small molecules. Additionally, sorafenib has shown preliminary activity in combination with chemotherapy and with epidermal growth factor receptor inhibitors. Future directions will include the development of rational combinations either with cytotoxic compounds or biologically targeted compounds and the identification of subsets of patients that might benefit from the other targets of sorafenib.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Benzenesulfonates/administration & dosage ; Benzenesulfonates/adverse effects ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/mortality ; Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Non-Small-Cell Lung/secondary ; Female ; Follow-Up Studies ; Forecasting ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/mortality ; Lung Neoplasms/pathology ; Male ; Neoplasm Staging ; Neovascularization, Pathologic/prevention & control ; Niacinamide/analogs & derivatives ; Phenylurea Compounds ; Pyridines/administration & dosage ; Pyridines/adverse effects ; Randomized Controlled Trials as Topic ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors ; Risk Assessment ; Survival Analysis ; Treatment Outcome ; Vascular Endothelial Growth Factors/antagonists & inhibitors
Chemical Substances	Benzenesulfonates ; Phenylurea Compounds ; Pyridines ; Vascular Endothelial Growth Factors ; Niacinamide (25X51I8RD4) ; sorafenib (9ZOQ3TZI87) ; Receptors, Vascular Endothelial Growth Factor (EC 2.7.10.1)
Language	English
Publishing date	2008-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2432037-7
ISSN	1556-1380 ; 1556-0864
ISSN (online)	1556-1380
ISSN	1556-0864
DOI	10.1097/JTO.0b013e318174e085
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Book: Quest for the cure

Blumenschein, George R

reflections on the evolution of breast cancer treatment

2014

Author's details	George R. Blumenschein
MeSH term(s)	Breast Neoplasms/therapy
Language	English
Size	xv, 84 pages :, illustrations, portraits
Document type	Book
ISBN	9780124201538 ; 0124201539
Database	Catalogue of the US National Library of Medicine (NLM)

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Book ; Online: Quest for the cure

Blumenschein, George R

reflections on the evolution of breast cancer treatment

2014

Abstract: This original fourteen chapter book is a brief, slightly autobiographic tale of medical oncologists, surgeons, radiation oncologists, and breast cancer patients in a well-established cancer center in Texas, who pursued the goal of cure for breast cancer. ...

Author's details	George R. Blumenschein, MD
Abstract	This original fourteen chapter book is a brief, slightly autobiographic tale of medical oncologists, surgeons, radiation oncologists, and breast cancer patients in a well-established cancer center in Texas, who pursued the goal of cure for breast cancer. The evolution of improved outcomes in the treatment of microscopic metastatic breast cancer is also the story of the development of adjuvant chemotherapy for post-operative breast disease. The adjuvant therapy of breast cancer came about with the realization that this malignancy, when diagnosed in most patients, had spread beyond the confines
Keywords	Breast/Cancer ; Breast/Cancer/Treatment ; Breast/Cancer/Treatment/History
Language	English
Size	Online-Ressource (108 pages), illustrations
Publisher	Elsevier/Academic Press
Publishing place	Amsterdam
Document type	Book ; Online
Note	Description based upon print version of record
ISBN	130607083X ; 9780124201538 ; 9781306070836 ; 0124201539
Database	Former special subject collection: coastal and deep sea fishing

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Book ; Online: Quest for the cure

Blumenschein, George R

reflections on the evolution of breast cancer treatment

2014

Author's details	George R. Blumenschein, MD
Abstract	This original fourteen chapter book is a brief, slightly autobiographic tale of medical oncologists, surgeons, radiation oncologists, and breast cancer patients in a well-established cancer center in Texas, who pursued the goal of cure for breast cancer. The evolution of improved outcomes in the treatment of microscopic metastatic breast cancer is also the story of the development of adjuvant chemotherapy for post-operative breast disease. The adjuvant therapy of breast cancer came about with the realization that this malignancy, when diagnosed in most patients, had spread beyond the confines
Keywords	Breast/Cancer ; Breast/Cancer/Treatment ; Breast/Cancer/Treatment/History
Language	English
Size	Online-Ressource (108 pages), illustrations
Publisher	Elsevier/Academic Press
Publishing place	Amsterdam
Document type	Book ; Online
Note	Description based upon print version of record
ISBN	130607083X ; 9780124201538 ; 9781306070836 ; 0124201539
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Article ; Online: Generalizability of ORIENT-11 trial results to a US standard-of-care cohort with advanced non-small-cell lung cancer.

Nagasaka, Misako / Molife, Cliff / Cui, Zhanglin Lin / Stefaniak, Victoria / Li, Xiaohong / Kim, Sangmi / Lee, Hsui-Yung / Beyrer, Julia / Blumenschein, George

Future oncology (London, England)

2022 Volume 18, Issue 16, Page(s) 1963–1977

Abstract: Aim: ...

Abstract	Aim:
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Carcinoma, Non-Small-Cell Lung/pathology ; Humans ; Lung Neoplasms/pathology ; Pemetrexed/therapeutic use ; Platinum/therapeutic use ; Retrospective Studies
Chemical Substances	Pemetrexed (04Q9AIZ7NO) ; Platinum (49DFR088MY)
Language	English
Publishing date	2022-03-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2274956-1
ISSN	1744-8301 ; 1479-6694
ISSN (online)	1744-8301
ISSN	1479-6694
DOI	10.2217/fon-2022-0099
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A Phase I Trial of Bevacizumab and Temsirolimus in Combination With Valproic Acid in Advanced Solid Tumors.

Nelson, Blessie Elizabeth / Tsimberidou, Apostolia M / Fu, Xueyao / Fu, Siqing / Subbiah, Vivek / Sood, Anil K / Rodon, Jordi / Karp, Daniel D / Blumenschein, George / Kopetz, Scott / Pant, Shubham / Piha-Paul, Sarina A

The oncologist

2023 Volume 28, Issue 12, Page(s) 1100–e1292

Abstract: Background: Preclinical models suggest synergy between anti-angiogenesis therapy, mammalian target of rapamycin (mTOR), and histone deacetylase inhibitors to promote anticancer activity.: Methods: This phase I study enrolled 47 patients between April ...

Abstract	Background: Preclinical models suggest synergy between anti-angiogenesis therapy, mammalian target of rapamycin (mTOR), and histone deacetylase inhibitors to promote anticancer activity. Methods: This phase I study enrolled 47 patients between April 2012 and 2018 and determined safety, maximum tolerated dose (MTD), and dose-limiting toxicities (DLTs) when combining bevacizumab, temsirolimus, and valproic acid in patients with advanced cancer. Results: Median age of enrolled patients was 56 years. Patients were heavily pretreated with a median of 4 lines of prior therapy. Forty-five patients (95.7%) experienced one or more treatment-related adverse events (TRAEs). Grade 3 TRAEs were lymphopenia (14.9%), thrombocytopenia (8.5%), and mucositis (6.4%). Grade 4 TRAEs included lymphopenia (2.1%) and CNS cerebrovascular ischemia (2.1%). Six patients developed DLTs across 10 dose levels with grade 3 infection, rash, mucositis, bowel perforation, elevated lipase, and grade 4 cerebrovascular ischemia. The MTD was dose level 9 (bevacizumab 5 mg/kg days 1 and 15 intravenously (IV) plus temsirolimus 25 mg days 1, 8, 15, and 22 IV and valproic acid 5 mg/kg on days 1-7 and 15-21 per orally (PO)). Objective response rate (ORR) was 7.9% with confirmed partial response (PRs) in 3 patients (one each in parotid gland, ovarian, and vaginal cancers). Stable disease (SD) ≥+6 months was seen in 5 patients (13.1%). Clinical benefit state (CBR: PR + SD ≥+6 months) was 21%. Conclusion: Combination therapy with bevacizumab, temsirolimus, and valproic acid was feasible, but there were numerous toxicities, which will require careful management for future clinical development (ClinicalTrials.gov Identifier: NCT01552434).
MeSH term(s)	Female ; Humans ; Middle Aged ; Bevacizumab/adverse effects ; Valproic Acid/adverse effects ; Mucositis ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Neoplasms/drug therapy ; Neoplasms/pathology ; Thrombocytopenia/drug therapy ; Lymphopenia ; Ischemia/drug therapy ; Ischemia/etiology ; Maximum Tolerated Dose
Chemical Substances	Bevacizumab (2S9ZZM9Q9V) ; temsirolimus (624KN6GM2T) ; Valproic Acid (614OI1Z5WI)
Language	English
Publishing date	2023-06-09
Publishing country	England
Document type	Clinical Trial, Phase I ; Journal Article
ZDB-ID	1409038-7
ISSN	1549-490X ; 1083-7159
ISSN (online)	1549-490X
ISSN	1083-7159
DOI	10.1093/oncolo/oyad158
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Zs.MO 494: Show issues

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