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Article: New strategies to maximize therapeutic opportunities for NAMPT inhibitors in oncology.

Roulston, Anne / Shore, Gordon C

Molecular & cellular oncology

2015 Volume 3, Issue 1, Page(s) e1052180

Abstract: Nicotinamide phosphoribosyltransferase (NAMPT) is crucial for nicotinamide adenine dinucleotide (NAD(+)) biosynthesis in mammalian cells. NAMPT inhibitors represent multifunctional anticancer agents that act on NAD(+) metabolism to shut down glycolysis, ... ...

Abstract	Nicotinamide phosphoribosyltransferase (NAMPT) is crucial for nicotinamide adenine dinucleotide (NAD(+)) biosynthesis in mammalian cells. NAMPT inhibitors represent multifunctional anticancer agents that act on NAD(+) metabolism to shut down glycolysis, nucleotide biosynthesis, and ATP generation and act indirectly as PARP and sirtuin inhibitors. The selectivity of NAMPT inhibitors preys on the increased metabolic requirements to replenish NAD(+) in cancer cells. Although initial clinical studies with NAMPT inhibitors did not achieve single-agent therapeutic levels before dose-limiting toxicities were reached, a new understanding of alternative rescue pathways and a biomarker that can be used to select patients provides new opportunities to widen the therapeutic window and achieve efficacious doses in the clinic. Recent work has also illustrated the potential for drug combination strategies to further enhance the therapeutic opportunities. This review summarizes recent discoveries in NAD(+)/NAMPT inhibitor biology in the context of exploiting this new knowledge to optimize the clinical outcomes for this promising new class of agents.
Language	English
Publishing date	2015-06-10
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2372-3556
ISSN	2372-3556
DOI	10.1080/23723556.2015.1052180
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Article ; Online: Apoptosis: it's BAK to VDAC.

Shore, Gordon C

EMBO reports

2009 Volume 10, Issue 12, Page(s) 1311–1313

MeSH term(s)	Animals ; Apoptosis/genetics ; Apoptosis/physiology ; Humans ; Mitochondrial Membranes/metabolism ; Mitochondrial Membranes/physiology ; Models, Biological ; Permeability ; Voltage-Dependent Anion Channels/genetics ; Voltage-Dependent Anion Channels/physiology ; bcl-2 Homologous Antagonist-Killer Protein/genetics ; bcl-2 Homologous Antagonist-Killer Protein/physiology ; bcl-2-Associated X Protein/genetics ; bcl-2-Associated X Protein/metabolism ; bcl-2-Associated X Protein/physiology
Chemical Substances	Voltage-Dependent Anion Channels ; bcl-2 Homologous Antagonist-Killer Protein ; bcl-2-Associated X Protein
Language	English
Publishing date	2009-11-13
Publishing country	England
Document type	Comment ; Journal Article ; Review
ZDB-ID	2020896-0
ISSN	1469-3178 ; 1469-221X
ISSN (online)	1469-3178
ISSN	1469-221X
DOI	10.1038/embor.2009.249
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Zs.A 5433: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Treatment of Low-grade Intermediate-risk Nonmuscle-invasive Bladder Cancer With UGN-102 ± Transurethral Resection of Bladder Tumor Compared to Transurethral Resection of Bladder Tumor Monotherapy: A Randomized, Controlled, Phase 3 Trial (ATLAS).

The Journal of urology

2023 Volume 210, Issue 4, Page(s) 619–629

Abstract: Purpose: Low-grade intermediate-risk nonmuscle-invasive bladder cancer is a chronic illness commonly treated by repetitive transurethral resection of bladder tumor. We compared the efficacy and safety of intravesical chemoablation with UGN-102 (a ... ...

Abstract	Purpose: Low-grade intermediate-risk nonmuscle-invasive bladder cancer is a chronic illness commonly treated by repetitive transurethral resection of bladder tumor. We compared the efficacy and safety of intravesical chemoablation with UGN-102 (a reverse thermal gel containing mitomycin), with or without subsequent transurethral resection of bladder tumor, to transurethral resection of bladder tumor alone in patients with low-grade intermediate-risk nonmuscle-invasive bladder cancer. Materials and methods: This prospective, randomized, phase 3 trial recruited patients with new or recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer to receive initial treatment with either UGN-102 once weekly for 6 weeks or transurethral resection of bladder tumor. Patients were followed quarterly by endoscopy, cytology, and for-cause biopsy. The primary end point was disease-free survival. All patients were followed for adverse events. Results: Trial enrollment was halted by the sponsor to pursue an alternative development strategy after 282 of a planned 632 patients were randomized to UGN-102 ± subsequent transurethral resection of bladder tumor (n=142) or transurethral resection of bladder tumor monotherapy (n=140), rendering the trial underpowered to perform hypothesis testing. Patients were predominantly male and ≥65 years of age. Tumor-free complete response 3 months after initial treatment was achieved by 92 patients (65%) who received UGN-102 and 89 patients (64%) treated by transurethral resection of bladder tumor. The estimated probability of disease-free survival 15 months after randomization was 72% for UGN-102 ± transurethral resection of bladder tumor and 50% for transurethral resection of bladder tumor (hazard ratio 0.45). The most common adverse events (incidence ≥10%) in the UGN-102 group were dysuria, micturition urgency, nocturia, and pollakiuria. Conclusions: Primary, nonsurgical chemoablation with UGN-102 for the management of low-grade intermediate-risk nonmuscle-invasive bladder cancer offers a potential therapeutic alternative to immediate transurethral resection of bladder tumor monotherapy and warrants further investigation.
MeSH term(s)	Humans ; Male ; Female ; Prospective Studies ; Transurethral Resection of Bladder ; Urinary Bladder Neoplasms/drug therapy ; Urinary Bladder Neoplasms/surgery ; Urologic Surgical Procedures ; Mitomycin/therapeutic use ; Administration, Intravesical ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/pathology
Chemical Substances	Mitomycin (50SG953SK6)
Language	English
Publishing date	2023-08-07
Publishing country	United States
Document type	Randomized Controlled Trial ; Clinical Trial, Phase III ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3176-8
ISSN	1527-3792 ; 0022-5347
ISSN (online)	1527-3792
ISSN	0022-5347
DOI	10.1097/JU.0000000000003645
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Article ; Online: Novel NAPRT specific antibody identifies small cell lung cancer and neuronal cancers as promising clinical indications for a NAMPT inhibitor/niacin co-administration strategy.

Cole, Jonathan / Guiot, Marie-Christine / Gravel, Michel / Bernier, Cynthia / Shore, Gordon C / Roulston, Anne

Oncotarget

2017 Volume 8, Issue 44, Page(s) 77846–77859

Abstract: Tumor cells are particularly dependent on ... ...

Abstract	Tumor cells are particularly dependent on NAD
Language	English
Publishing date	2017-09-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.20840
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Article ; Online: BIM, PUMA, and the achilles' heel of oncogene addiction.

Roulston, Anne / Muller, William J / Shore, Gordon C

Science signaling

2013 Volume 6, Issue 268, Page(s) pe12

Abstract: Cancer cells undergo extensive genetic and epigenetic rewiring to support the malignant phenotype, and yet cell survival and proliferation often remain dependent on one or a limited number of driver mutations. This is the concept of oncogene addiction, ... ...

Abstract	Cancer cells undergo extensive genetic and epigenetic rewiring to support the malignant phenotype, and yet cell survival and proliferation often remain dependent on one or a limited number of driver mutations. This is the concept of oncogene addiction, the elucidation of which has led to substantial progress in therapeutic interventions. However, because resistance mechanisms often emerge, explicating the pathways that connect therapeutic oncogene inactivation to the cell death machinery is critical to exploiting additional synthetic lethal opportunities.
MeSH term(s)	Apoptosis Regulatory Proteins/genetics ; Bcl-2-Like Protein 11 ; Cell Proliferation ; Cell Survival/genetics ; Drug Delivery Systems/methods ; Drug Resistance, Neoplasm/genetics ; Humans ; Membrane Proteins/genetics ; Models, Biological ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/physiopathology ; Oncogenes/genetics ; Proto-Oncogene Proteins/genetics ; Receptor, ErbB-2/genetics ; Signal Transduction/genetics
Chemical Substances	Apoptosis Regulatory Proteins ; BBC3 protein, human ; BCL2L11 protein, human ; Bcl-2-Like Protein 11 ; Membrane Proteins ; Proto-Oncogene Proteins ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2013-03-26
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2417226-1
ISSN	1937-9145 ; 1945-0877
ISSN (online)	1937-9145
ISSN	1945-0877
DOI	10.1126/scisignal.2004113
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Article ; Online: Real-World Prostate-Specific Antigen Response and Treatment Adherence of Apalutamide in Patients With Non-Metastatic Castration-Resistant Prostate Cancer.

Lowentritt, Benjamin / Brown, Gordon / Pilon, Dominic / Ellis, Lorie / Germain, Guillaume / Rossi, Carmine / Lefebvre, Patrick / Kernen, Kenneth / Sieber, Paul / Shore, Neal

Urology

2022 Volume 166, Page(s) 182–188

Abstract: Objective: To describe prostate-specific antigen (PSA) response and treatment adherence, overall and stratified by race, for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) treated with apalutamide.: Methods: Electronic ... ...

Abstract	Objective: To describe prostate-specific antigen (PSA) response and treatment adherence, overall and stratified by race, for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) treated with apalutamide. Methods: Electronic medical records representing 63 urology practices from the United States were used to conduct this study. Patients with ≥2 apalutamide prescription fills and ≥12 months of prior prostate cancer management were identified. Patients were followed from apalutamide initiation until a switch to another antineoplastic treatment, death, or end of data availability (October 4, 2019). PSA response (≥50% decline from baseline PSA) and apalutamide adherence rates are described for the overall nmCRPC population treated and also stratified by race (Black and non-Black cohorts). Results: Overall, 193 patients with nmCRPC were initiated on apalutamide. Thirty-three patients were Black (17.1%), 138 were non-Black (71.5%), and the remaining had an unknown racial background. The mean baseline PSA level for the overall, Black, and non-Black cohorts, was 7.0 ng/mL, 10.5 ng/mL, and 5.6 ng/mL, respectively. At 12 months of follow-up, PSA response was 86.0%, 93.1%, and 85.9% for the overall, Black, and non-Black cohorts, respectively. During a mean follow-up period of 333 days, 352 days, and 326 days, adherence was 93.6%, 90.1%, and 94.5% for the overall, Black and non-Black cohorts, respectively. Conclusion: This real-world study of patients with nmCRPC initiated on apalutamide showed that PSA response was robust and consistent with clinical trial data. Moreover, both Black and non-Black patients demonstrated high treatment adherence.
MeSH term(s)	Humans ; Male ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/pathology ; Thiohydantoins ; Treatment Adherence and Compliance
Chemical Substances	Thiohydantoins ; apalutamide ; Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2022-03-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	192062-5
ISSN	1527-9995 ; 0090-4295
ISSN (online)	1527-9995
ISSN	0090-4295
DOI	10.1016/j.urology.2022.02.024
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Zs.A 1142: 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)
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Article ; Online: Bcl-2 proteins and apoptosis: choose your partner.

Shore, Gordon C / Nguyen, Mai

Cell

2008 Volume 135, Issue 6, Page(s) 1004–1006

Abstract: The Bcl-2 family protein Bax is a key effector of apoptosis. Lovell et al. (2008) now describe the reconstitution and regulation in liposomes of tBid-mediated membrane penetration and oligomerization of Bax. These and other recent studies shed new light ... ...

Abstract	The Bcl-2 family protein Bax is a key effector of apoptosis. Lovell et al. (2008) now describe the reconstitution and regulation in liposomes of tBid-mediated membrane penetration and oligomerization of Bax. These and other recent studies shed new light on the control of permeabilization of the mitochondrial outer membrane during apoptosis.
MeSH term(s)	Animals ; Apoptosis ; Liposomes/metabolism ; Mitochondrial Membranes/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism
Chemical Substances	Liposomes ; Proto-Oncogene Proteins c-bcl-2
Language	English
Publishing date	2008-12-12
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2008.11.029
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Zs.A 1167: 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)
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Article ; Online: Perceptions of safety culture and recording in the operating room: understanding barriers to video data capture.

Gordon, Lauren / Reed, Cheyanne / Sorensen, Jette Led / Schulthess, Pansy / Strandbygaard, Jeanett / Mcloone, Mary / Grantcharov, Teodor / Shore, Eliane M

Surgical endoscopy

2021 Volume 36, Issue 6, Page(s) 3789–3797

Abstract: Objective: Recording in the operating room is an important tool to help surgical teams improve their performance. This is becoming more feasible using the Operating Room Black Box, a comprehensive data capture platform. Operating room (OR) staff, ... ...

Abstract	Objective: Recording in the operating room is an important tool to help surgical teams improve their performance. This is becoming more feasible using the Operating Room Black Box, a comprehensive data capture platform. Operating room (OR) staff, however, may voice reasonable concerns as recording initiatives are implemented. The objective of this study was to assess pre-implementation attitudes of OR staff toward operative recording and explore the relationship of these attitudes to the themes of (1) safety culture, (2) impostor syndrome, and (3) privacy concerns. Methods: This cross-sectional survey study measured staff members' beliefs and opinions of operative recording and used three previously validated tools (safety attitudes questionnaire, clance impostor phenomenon scale, and dispositional privacy concern) to assess personal and professional factors. Concepts were correlated using Pearson's correlation coefficient. Results: Forty-three staff members participated in this study, with a response rate of 45% (n = 43/96, 20/22 nurses, 9/11 gynecologists, 14/63 anesthesiologists). Opinions of operative data capture were generally positive (5-point Likert scale, mean = 3.81, SD = 0.91). Nurses tended to have more favorable opinions of the OR Black Box as compared to gynecologists and anesthesiologists, though this did not reach statistical significance (4.15 vs. 3.67 vs 3.43, p = 0.06). Impostor syndrome characteristics correlated with concerns about litigation related to recording (r = - 0.32, p = 0.04). Conclusion: There are personal and professional attributes of the OR team that impact perceptions of the OR Black Box and implications around privacy and litigation. Addressing these concerns may facilitate successful implementation of the OR Black Box and improve team communication and patient safety in the OR.
MeSH term(s)	Anxiety Disorders ; Attitude of Health Personnel ; Cross-Sectional Studies ; Humans ; Operating Rooms ; Patient Care Team ; Patient Safety ; Safety Management ; Self Concept
Language	English
Publishing date	2021-10-04
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639039-0
ISSN	1432-2218 ; 0930-2794
ISSN (online)	1432-2218
ISSN	0930-2794
DOI	10.1007/s00464-021-08695-5
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Article ; Online: BCL2-CISD2: An ER complex at the nexus of autophagy and calcium homeostasis?

Chang, Natasha C / Nguyen, Mai / Shore, Gordon C

Autophagy

2012 Volume 8, Issue 5, Page(s) 856–857

Abstract: CISD2, an ER BCL2-associated autophagy regulator also known as NAF-1, is responsible for the human degenerative disorder Wolfram Syndrome 2. In order to interrogate the physiological role of CISD2 we generated and characterized the Cisd2 gene deletion in ...

Abstract	CISD2, an ER BCL2-associated autophagy regulator also known as NAF-1, is responsible for the human degenerative disorder Wolfram Syndrome 2. In order to interrogate the physiological role of CISD2 we generated and characterized the Cisd2 gene deletion in mice. Cisd2 null mice manifest significant degeneration in skeletal muscle tissues, which is accompanied with augmented autophagy, dysregulated Ca ( 2+) homeostasis and elongated mitochondria. Our findings describe a novel role for BCL2-CISD2 in the homeostatic maintenance of skeletal muscle. It remains to be elucidated how and if the antagonism of the BECN1 autophagy-initiating complex and modulation of ER Ca ( 2+) homeostasis by BCL2-CISD2 are interconnected.
MeSH term(s)	Animals ; Autophagy ; Calcium/metabolism ; Calcium Signaling ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Endoplasmic Reticulum/metabolism ; Homeostasis ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Mice ; Models, Biological ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism
Chemical Substances	Carrier Proteins ; Inositol 1,4,5-Trisphosphate Receptors ; Nerve Tissue Proteins ; Noxp70 protein, mouse ; Proto-Oncogene Proteins c-bcl-2 ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2012-05-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.4161/auto.20054
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Article: Unique biology of Mcl-1: therapeutic opportunities in cancer.

Warr, Matthew R / Shore, Gordon C

Current molecular medicine

2008 Volume 8, Issue 2, Page(s) 138–147

Abstract: Accumulating evidence suggests that Mcl-1 plays a critical pro-survival role in the development and maintenance of both normal and malignant tissues. Regulation of Mcl-1 expression occurs at multiple levels, allowing for either the rapid induction or ... ...

Abstract	Accumulating evidence suggests that Mcl-1 plays a critical pro-survival role in the development and maintenance of both normal and malignant tissues. Regulation of Mcl-1 expression occurs at multiple levels, allowing for either the rapid induction or elimination of the protein in response to different cellular events. This suggests that Mcl-1 can play an early role in response to signals directing either cell survival or cell death. Deregulation of pathways regulating Mcl-1 that result in its over-expression likely contribute to a cell's inability to properly respond to death signals possibly leading to cell immortalization and tumorigenic conversion. Correspondingly, Mcl-1 has been shown to be up-regulated in numerous hematological and solid tumor malignancies. Moreover, this up-regulation appears to be a factor in the resistance of some cancer types to conventional cancer therapies. Mechanisms that abrogate the pro-survival function of Mcl-1 either by diminishing its levels or inactivating its functional BH3 groove have shown promise for the combinational treatment with existing cancer therapies and as single agents in certain malignancies. Here we review the various pathways that regulate Mcl-1 expression and describe agents that are currently under development to modulate Mcl-1 activity for therapeutic benefit in oncology.
MeSH term(s)	Animals ; Humans ; Models, Biological ; Myeloid Cell Leukemia Sequence 1 Protein ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Neoplasms/drug therapy ; Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors ; Proto-Oncogene Proteins c-bcl-2/genetics ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Signal Transduction
Chemical Substances	Myeloid Cell Leukemia Sequence 1 Protein ; Neoplasm Proteins ; Proto-Oncogene Proteins c-bcl-2
Language	English
Publishing date	2008-02-22
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2064873-X
ISSN	1566-5240
ISSN	1566-5240
DOI	10.2174/156652408783769580
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