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Article ; Online: Targeting Mesothelin in Solid Tumours: Anti-mesothelin Antibody and Drug Conjugates.

Chu, Quincy

2023 Volume 25, Issue 4, Page(s) 309–323

Abstract: Purpose of review: This review aims to summarise the pathobiological role of mesothelin and the current data on therapeutic antibodies targeting mesothelin in solid tumours.: Recent findings: High mesothelin expression is restricted to the ... ...

Abstract	Purpose of review: This review aims to summarise the pathobiological role of mesothelin and the current data on therapeutic antibodies targeting mesothelin in solid tumours. Recent findings: High mesothelin expression is restricted to the pericardium, pleura, peritoneum and tunica vaginalis. Mesothelin does not seem to have any normal biological function in adult normal tissues. Mesothelin is highly expressed in mesothelioma, serous ovarian cancer, pancreatic cancer and some gastric cancer and adenocarcinoma of the lung and is responsible for tumour proliferation, metastasis, resistance to chemotherapy or radiation and evasion of immune system. To date, antibody, antibody drug conjugates and bispecific antibodies with immune checkpoints have been investigated in mesothelin expressing malignancies. After a couple of decades of clinical investigation in antibody targeting mesothelin, the therapeutic benefit is relatively modest. Novel delivery of mesothelin targeting agents, more potent payload in antibody drug conjugates and immune checkpoint inhibitor, may improve therapeutic benefit.
MeSH term(s)	Humans ; Adenocarcinoma/drug therapy ; GPI-Linked Proteins/metabolism ; GPI-Linked Proteins/therapeutic use ; Immunoconjugates/therapeutic use ; Pharmaceutical Preparations ; Mesothelin/immunology
Chemical Substances	GPI-Linked Proteins ; Immunoconjugates ; Pharmaceutical Preparations ; Mesothelin (J27WDC343N)
Language	English
Publishing date	2023-02-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057359-5
ISSN	1534-6269 ; 1523-3790
ISSN (online)	1534-6269
ISSN	1523-3790
DOI	10.1007/s11912-023-01367-8
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Article: Targeting non-small cell lung cancer: driver mutation beyond epidermal growth factor mutation and anaplastic lymphoma kinase fusion.

Chu, Quincy S

Therapeutic advances in medical oncology

2020 Volume 12, Page(s) 1758835919895756

Abstract: The identification of driver mutations in epidermal growth factor receptor, anaplastic lymphoma kinase, ... ...

Abstract	The identification of driver mutations in epidermal growth factor receptor, anaplastic lymphoma kinase, the
Language	English
Publishing date	2020-01-23
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2503443-1
ISSN	1758-8359 ; 1758-8340
ISSN (online)	1758-8359
ISSN	1758-8340
DOI	10.1177/1758835919895756
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Article ; Online: How Is Receptor Activator of Nuclear Factor-κβ/Receptor Activator of Nuclear Factor-κβ Ligand Targeting Ranked as an Immuno-Oncology Target for NSCLC: a Pathway Unclear as yet?

Chu, Quincy S C

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

2020 Volume 15, Issue 10, Page(s) 1561–1564

MeSH term(s)	Carcinoma, Non-Small-Cell Lung/drug therapy ; Humans ; Ligands ; Lung Neoplasms/drug therapy ; NF-kappa B ; Osteoprotegerin ; RANK Ligand ; Receptors, Cytoplasmic and Nuclear
Chemical Substances	Ligands ; NF-kappa B ; Osteoprotegerin ; RANK Ligand ; Receptors, Cytoplasmic and Nuclear
Language	English
Publishing date	2020-09-28
Publishing country	United States
Document type	Editorial
ZDB-ID	2432037-7
ISSN	1556-1380 ; 1556-0864
ISSN (online)	1556-1380
ISSN	1556-0864
DOI	10.1016/j.jtho.2020.07.011
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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: Response to a Letter Received Entitled: "'Brief Report: Canadian Cancer Trials Group IND.227': Unpacking the Clinical Potential of Single-Agent Pembrolizumab in Advanced Malignant Pleural Mesothelioma".

Piccirillo, Maria Carmela / Chu, Quincy / Bradbury, Penelope / Seymour, Lesley

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

2023 Volume 18, Issue 6, Page(s) e68–e69

MeSH term(s)	Humans ; Mesothelioma, Malignant/drug therapy ; Lung Neoplasms/drug therapy ; Lung Neoplasms/pathology ; Canada ; Antibodies, Monoclonal, Humanized/pharmacology ; Antibodies, Monoclonal, Humanized/therapeutic use
Chemical Substances	pembrolizumab (DPT0O3T46P) ; Antibodies, Monoclonal, Humanized
Language	English
Publishing date	2023-05-21
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2432037-7
ISSN	1556-1380 ; 1556-0864
ISSN (online)	1556-1380
ISSN	1556-0864
DOI	10.1016/j.jtho.2023.03.003
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Article ; Online: Present and Emerging Biomarkers in Immunotherapy for Metastatic Non-Small Cell Lung Cancer: A Review.

Khwaja, Raida M / Chu, Quincy S-C

Current oncology (Toronto, Ont.)

2022 Volume 29, Issue 2, Page(s) 479–489

Abstract: Targeting the immune system, especially the PDL-1/PD-1 axis, has significantly improved the outcomes of metastatic lung cancer patients. However, only a portion of patients will benefit significantly from PD(L)1 therapeutics alone or in combination with ... ...

Abstract	Targeting the immune system, especially the PDL-1/PD-1 axis, has significantly improved the outcomes of metastatic lung cancer patients. However, only a portion of patients will benefit significantly from PD(L)1 therapeutics alone or in combination with either chemotherapy or anti-CTLA4 antibody. It is therefore important to study predictive biomarkers to help select the patients who will experience the most benefit from immunotherapy. In this paper, the current status of PDL-1 expression on tumour cells, the smoking status of patients, tumour mutational burden, gut microbiome and STK11 and KEAP1 mutations in the tumour as predictive biomarkers for PD(L)-1-based immunotherapy are summarized.
MeSH term(s)	Biomarkers, Tumor/genetics ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Humans ; Immunotherapy ; Kelch-Like ECH-Associated Protein 1/genetics ; Kelch-Like ECH-Associated Protein 1/metabolism ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; NF-E2-Related Factor 2/metabolism ; NF-E2-Related Factor 2/therapeutic use
Chemical Substances	Biomarkers, Tumor ; Kelch-Like ECH-Associated Protein 1 ; NF-E2-Related Factor 2
Language	English
Publishing date	2022-01-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1236972-x
ISSN	1718-7729 ; 1198-0052
ISSN (online)	1718-7729
ISSN	1198-0052
DOI	10.3390/curroncol29020043
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Article ; Online: Application of liquid biopsy-based targeted capture sequencing analysis to improve the precision treatment of non-small cell lung cancer by tyrosine kinase inhibitors.

Zhang, Lei / Coffin, John / Formenti, Kim / Chu, Quincy / Izevbaye, Iyare

BMJ open respiratory research

2022 Volume 9, Issue 1

Abstract: Background: Targeted therapy of patients with non-small cell lung cancer (NSCLC) who harbour sensitising mutations by tyrosine kinase inhibitors (TKIs) has been found more effective than traditional chemotherapies. However, target genes status (eg, ... ...

Abstract	Background: Targeted therapy of patients with non-small cell lung cancer (NSCLC) who harbour sensitising mutations by tyrosine kinase inhibitors (TKIs) has been found more effective than traditional chemotherapies. However, target genes status (eg, epidermal growth factor receptor ( Methods: Plasma samples from patients with NSCLC who showed resistance to the first/second-generation Results: A total of 24 plasma cell-free DNA (cfDNA) samples were tested by the targeted capture sequencing assay. 33.3% (8/24) cfDNA samples were positive for Conclusion: The targeted capture sequencing test can support comprehensive molecular analysis needed for TKIs treatment, which is promising to be clinically applied for the improved precision treatment of NSCLC.
MeSH term(s)	Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Drug Resistance, Neoplasm/genetics ; ErbB Receptors/genetics ; ErbB Receptors/therapeutic use ; Humans ; Liquid Biopsy ; Lung Neoplasms/diagnosis ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Mutation ; Protein Kinase Inhibitors/therapeutic use
Chemical Substances	Protein Kinase Inhibitors ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2022-01-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2736454-9
ISSN	2052-4439 ; 2052-4439
ISSN (online)	2052-4439
ISSN	2052-4439
DOI	10.1136/bmjresp-2021-001154
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Article ; Online: Rapid Unmasking of Immune-related Adverse Events After Discontinuation of Chemotherapy in Chemo-immunotherapy Regimens.

Riopel, Nicholas D / Chu, Quincy / Walker, John / Ye, Carrie

Journal of immunotherapy (Hagerstown, Md. : 1997)

2022 Volume 45, Issue 4, Page(s) 207–209

Abstract: Pembrolizumab is an immune-checkpoint inhibitor (ICI) of programmed cell death protein 1 (PD-1), which restores T-cell-mediated antitumor immune activity and therefore enhances the body's immune response to cancer cells. Due to the nature of this therapy, ...

Abstract	Pembrolizumab is an immune-checkpoint inhibitor (ICI) of programmed cell death protein 1 (PD-1), which restores T-cell-mediated antitumor immune activity and therefore enhances the body's immune response to cancer cells. Due to the nature of this therapy, immune-related adverse events (irAE) can manifest in nearly every organ system. Chemo-immunotherapy regimens are now considered first-line treatment for several cancers, with recent literature suggesting there are higher rates of certain irAEs with ICI monotherapy when compared with chemo-immunotherapy combinations. In certain regimens chemo-immunotherapy induction is followed by ICI maintenance monotherapy, and data regarding irAE incidence in this transition period are very limited. We report 3 cases of patients on pembrolizumab in combination with cytotoxic chemotherapy who developed an irAE shortly following discontinuation of a chemotherapy agent. Cases were identified in the Rheumatology in Immuno-Oncology clinic at the University of Alberta and clinical data were extracted by retrospective chart review after obtaining written consent from individual patients. These findings demonstrate that chemotherapy may suppress irAEs in patients using ICIs, and that when chemotherapy agents in combined regimens are discontinued, irAEs can be "unmasked" within the following 6 weeks. Clinicians should be aware of this risk and monitor for irAE development during this critical time period. To the best of the authors' knowledge, this has not been previously reported in the literature.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Humans ; Immune Checkpoint Inhibitors ; Immunologic Factors/therapeutic use ; Immunotherapy/adverse effects ; Neoplasms/drug therapy ; Retrospective Studies
Chemical Substances	Antineoplastic Agents ; Immune Checkpoint Inhibitors ; Immunologic Factors
Language	English
Publishing date	2022-01-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	1064067-8
ISSN	1537-4513 ; 1053-8550 ; 1524-9557
ISSN (online)	1537-4513
ISSN	1053-8550 ; 1524-9557
DOI	10.1097/CJI.0000000000000409
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Article ; Online: Bilateral Lung Transplant for Treatment of Idiopathic Pulmonary Fibrosis With Undetected Lung Adenocarcinoma: A Case Report.

Jogiat, Uzair M / Chu, Quincy S / Nagendran, Jayan / Laing, Bryce / Hirji, Alim / Adam, Benjamin A

Anticancer research

2022 Volume 42, Issue 2, Page(s) 1157–1160

Abstract: Background: Lung transplant has become a curative therapy for various forms of progressive lung disease refractory to medical management. Idiopathic pulmonary fibrosis (IPF) is a rare condition characterized by accumulation of activated fibroblasts and ... ...

Abstract	Background: Lung transplant has become a curative therapy for various forms of progressive lung disease refractory to medical management. Idiopathic pulmonary fibrosis (IPF) is a rare condition characterized by accumulation of activated fibroblasts and secretion of extracellular matrices within the lung parenchyma. End-stage IPF is a fatal condition, with limited medical therapies other than lung transplantation. IPF has been demonstrated as a known risk factor for the development of lung cancer, and current lung transplant standards define history of malignancy within the past five years as an absolute exclusion criterion. Case report: We present the case of a patient with biopsy-confirmed idiopathic pulmonary fibrosis treated with bilateral lung transplant, discovered to have stage four lung adenocarcinoma in the explanted lungs. The patient subsequently received pseudoadjuvant chemotherapy and remained recurrence-free until 23 months post-transplant. Conclusion: This case highlights the challenge of ruling out malignancy in patients with end-stage lung disease. There remains a paucity of clinical studies on lung transplantation for lung cancer and more evidence is required before supporting this clinical decision.
MeSH term(s)	Adenocarcinoma of Lung/diagnosis ; Adenocarcinoma of Lung/drug therapy ; Adenocarcinoma of Lung/pathology ; Adult ; Canada ; Chemotherapy, Adjuvant ; Contraindications, Procedure ; Delayed Diagnosis ; Humans ; Idiopathic Pulmonary Fibrosis/drug therapy ; Idiopathic Pulmonary Fibrosis/surgery ; Lung Neoplasms/diagnosis ; Lung Neoplasms/drug therapy ; Lung Neoplasms/pathology ; Lung Transplantation/adverse effects ; Male ; Postoperative Period ; Time Factors
Language	English
Publishing date	2022-01-29
Publishing country	Greece
Document type	Case Reports ; Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.15580
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Article: Targeting Novel but Less Common Driver Mutations and Chromosomal Translocations in Advanced Non-Small Cell Lung Cancer.

Daoud, Alia / Chu, Quincy S

Frontiers in oncology

2017 Volume 7, Page(s) 222

Abstract: Discovery of the epidermal growth factor receptor gene mutation and the anaplastic lymphoma kinase chromosomal translocation in non-small cell lung cancer has prompted efforts around the world to identify many less common targetable oncogenic drivers. ... ...

Abstract	Discovery of the epidermal growth factor receptor gene mutation and the anaplastic lymphoma kinase chromosomal translocation in non-small cell lung cancer has prompted efforts around the world to identify many less common targetable oncogenic drivers. Such concerted efforts have been variably successful in both non-squamous and squamous cell carcinomas of the lung. Some of the targeted therapies for these oncogenic drivers have received regulatory approval for clinical use, while others have modest clinical benefit. In this mini-review, several of these targets will be reviewed.
Language	English
Publishing date	2017-09-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2017.00222
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Article ; Online: Risk stratification of gastrointestinal stromal tumors by Nanostring gene expression profiling.

Nowak, Klaudia / Formenti, Kim / Huang, Jingyang / Bigras, Gilbert / Chu, Quincy / Adam, Benjamin A / Izevbaye, Iyare

Journal of cancer research and clinical oncology

2022 Volume 148, Issue 6, Page(s) 1325–1336

Abstract: Purpose: The risk assessment classification schemes for gastrointestinal stromal tumors (GIST) include tumor site, size, mitotic count and variably tumor rupture. Heterogeneity in high-risk GIST poses limitations for current classification schemes. This ...

Abstract	Purpose: The risk assessment classification schemes for gastrointestinal stromal tumors (GIST) include tumor site, size, mitotic count and variably tumor rupture. Heterogeneity in high-risk GIST poses limitations for current classification schemes. This study aims to demonstrate the clinical utility of risk stratification by gene expression profiling (GEP) using Nanostring technology. Methods: Fifty-six GIST cases were analyzed using a 231 gene expression panel. GEP results were correlated with clinical and pathological data. The prognostic performance was assessed in 34 patients with available survival data using ROC curves, Kaplan-Meier survival curves and compared with traditional risk assessment schemes. Volcano plot analysis identified seven genes with significantly higher expression (FDR < .0.05) in high-risk than in non-high-risk tumors, namely TYMS, CDC2, TOP2A, CCNA2, E2F1, PCNA, and BIRC5. Together, these transcripts exhibited significantly higher expression in high-risk tumors than in intermediate (P < 0.01), low (P < 0.001), and very low (P = 0.01) risk tumors. Receiver-operating characteristic curve analysis demonstrated area under the curve (AUC) to be 0.858 for the separation of high-risk and non-high-risk tumors. Kaplan-Meier survival analysis demonstrated improved risk stratification (log-rank test P < 0.001) compared to the current risk assessment classification (P = 0.231). Conclusion: In addition to current clinical and histology-based risk classification for patients with GIST, gene expression may offer complementary prognostic information.
MeSH term(s)	Gastrointestinal Stromal Tumors/genetics ; Gastrointestinal Stromal Tumors/pathology ; Gene Expression Profiling ; Humans ; Neoplasm Recurrence, Local/pathology ; Prognosis ; Retrospective Studies ; Risk Assessment/methods
Language	English
Publishing date	2022-01-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-022-03924-3
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