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Article ; Online: Copy Number Analysis in Cancer Diagnostic Testing.

Spence, Tara / Dubuc, Adrian M

2022 Volume 42, Issue 3, Page(s) 451–468

Abstract: Accurate detection of copy number alterations (CNAs) has become increasingly important in clinical oncology for the purpose of diagnosis, prognostication, and disease management. Cytogenetic approaches for the detection of CNAs, including karyotype, ... ...

Abstract	Accurate detection of copy number alterations (CNAs) has become increasingly important in clinical oncology for the purpose of diagnosis, prognostication, and disease management. Cytogenetic approaches for the detection of CNAs, including karyotype, fluorescence in situ hybridization (FISH), and chromosomal microarray, remain mainstays in clinical laboratories. Yet, with rapidly decreasing costs and improved accuracy of CNA detection using emerging technologies such as next-generation sequencing and optical genome mapping, we are approaching a new era of cytogenomics and molecular oncology. The aim of this review is to describe the benefits and limitations associated with the routine clinical application of available classic, emerging, and projected future technologies for the detection of CNAs in oncology.
MeSH term(s)	DNA Copy Number Variations ; High-Throughput Nucleotide Sequencing ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Neoplasms/diagnosis ; Neoplasms/genetics
Language	English
Publishing date	2022-08-22
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604580-7
ISSN	1557-9832 ; 0272-2712
ISSN (online)	1557-9832
ISSN	0272-2712
DOI	10.1016/j.cll.2022.05.003
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Article ; Online: Very Low Vitamin D in a Patient With a Novel Pathogenic Variant in the

Banerjee, Ronadip R / Spence, Tara / Frank, Stuart J / Pandian, Raj / Hoofnagle, Andrew N / Argiropoulos, Bob / Marcadier, Julien L

Journal of the Endocrine Society

2021 Volume 5, Issue 9, Page(s) bvab104

Abstract: Circulating plasma vitamin D metabolites are highly bound to vitamin D-binding protein (DBP), also known ... ...

Abstract	Circulating plasma vitamin D metabolites are highly bound to vitamin D-binding protein (DBP), also known as
Language	English
Publishing date	2021-06-05
Publishing country	United States
Document type	Case Reports
ISSN	2472-1972
ISSN (online)	2472-1972
DOI	10.1210/jendso/bvab104
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Article ; Online: MicroRNAs in extracellular vesicles: potential cancer biomarkers.

Kinoshita, Takashi / Yip, Kenneth W / Spence, Tara / Liu, Fei-Fei

Journal of human genetics

2017 Volume 62, Issue 1, Page(s) 67–74

Abstract: Extracellular vesicles (EV) are small membrane-bound structures that are secreted by various cell types, including tumor cells. Recent studies have shown that EVs are important for cell-to-cell communication, locally and distantly; horizontally ... ...

Abstract	Extracellular vesicles (EV) are small membrane-bound structures that are secreted by various cell types, including tumor cells. Recent studies have shown that EVs are important for cell-to-cell communication, locally and distantly; horizontally transferring DNA, mRNA, microRNA (miRNA), proteins and lipids. In the context of cancer biology, tumor-derived EVs are capable of modifying the microenvironment, promoting tumor progression, immune evasion, angiogenesis and metastasis. miRNAs contained within EVs are functionally associated with cancer progression, metastasis and aggressive tumor phenotypes. These factors, along with their stability in bodily fluids, have led to extensive investigations on the potential role of circulating EV-derived miRNAs as tumor biomarkers. In this review, we summarize the current understanding of circulating EV miRNAs in human cancer, and discuss their clinical utility and challenges in functioning as biomarkers.
MeSH term(s)	Biomarkers, Tumor/genetics ; Cell-Derived Microparticles/genetics ; Exosomes/genetics ; Extracellular Vesicles/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/genetics ; Neoplasms/genetics ; Neoplasms/pathology ; Tumor Microenvironment/genetics
Chemical Substances	Biomarkers, Tumor ; MicroRNAs
Language	English
Publishing date	2017-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1425192-9
ISSN	1435-232X ; 1434-5161
ISSN (online)	1435-232X
ISSN	1434-5161
DOI	10.1038/jhg.2016.87
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Article ; Online: Clinical implementation of circulating tumour DNA testing for

Spence, Tara / Perera, Sheron / Weiss, Jessica / Grenier, Sylvie / Ranich, Laura / Shepherd, Frances / Stockley, Tracy L

Journal of clinical pathology

2020 Volume 74, Issue 2, Page(s) 91–97

Abstract: Aims: Epidermal growth factor receptor (: Methods: Using droplet digital PCR (ddPCR), we examined the : Results: Of the 343 patients with liquid biopsy test results, 24% were T790M positive. No clear clinical correlation with a T790M positive test ...

Abstract	Aims: Epidermal growth factor receptor ( Methods: Using droplet digital PCR (ddPCR), we examined the Results: Of the 343 patients with liquid biopsy test results, 24% were T790M positive. No clear clinical correlation with a T790M positive test result was identified in this study, although the number of metastatic sites did correlate significantly with the presence of Conclusions: The ddPCR test for
MeSH term(s)	Acrylamides/therapeutic use ; Adult ; Aged ; Aniline Compounds/therapeutic use ; Antineoplastic Agents/therapeutic use ; Carcinoma, Non-Small-Cell Lung/blood ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Circulating Tumor DNA/blood ; Circulating Tumor DNA/genetics ; Drug Resistance, Neoplasm/genetics ; ErbB Receptors/genetics ; Female ; Humans ; Liquid Biopsy/methods ; Lung Neoplasms/blood ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Male ; Middle Aged ; Mutation ; Patient Selection ; Polymerase Chain Reaction/methods
Chemical Substances	Acrylamides ; Aniline Compounds ; Antineoplastic Agents ; Circulating Tumor DNA ; osimertinib (3C06JJ0Z2O) ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2020-05-29
Publishing country	England
Document type	Journal Article
ZDB-ID	80261-x
ISSN	1472-4146 ; 0021-9746
ISSN (online)	1472-4146
ISSN	0021-9746
DOI	10.1136/jclinpath-2020-206668
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Article ; Online: MicroRNAs in nasopharyngeal carcinoma.

Spence, Tara / Bruce, Jeff / Yip, Kenneth W / Liu, Fei-Fei

Chinese clinical oncology

2016 Volume 5, Issue 2, Page(s) 17

Abstract: It is becoming increasingly evident that aberrantly expressed microRNAs (miRNAs) are responsible for a number of disease processes, including cancer initiation and progression. miRNAs have been implicated as key players in numerous neoplasms, including ... ...

Abstract	It is becoming increasingly evident that aberrantly expressed microRNAs (miRNAs) are responsible for a number of disease processes, including cancer initiation and progression. miRNAs have been implicated as key players in numerous neoplasms, including nasopharyngeal carcinoma (NPC). Functionally, deregulation of miRNAs that act either as tumour suppressors or oncogenes results in numerous cancer-associated phenomena, including changes in proliferation, migration, and cell survival. Furthermore, miRNA expression has been associated with chemoresistant or radioresistant phenotypes; highlighting the importance of miRNAs in mediating oncogenic processes. Prognostic and predictive miRNA signatures have been defined for a variety of cancer types, including NPC, whereby these signatures offer a potentially important clinical tool for assessing the disease state, as well as predicting treatment response and clinical outcome. Therefore, further examination and validation of miRNAs that are deregulated in NPC will provide insight into the fundamental drivers of this disease, which will aid in the identification of novel targeted treatments. This review summarizes recent advances in the study of miRNAs in NPC, with specific discussion on the role of miRNAs in NPC pathogenesis and the potential utility of miRNAs as prognostic biomarkers. Our increasing understanding of the role of miRNAs in NPC tumorigenesis and their application as novel biomarkers will undoubtedly prove useful in the stratification of future patients into clinically relevant treatment classifications, thereby improving and personalizing disease management.
MeSH term(s)	Biomarkers, Tumor/genetics ; Carcinoma ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Herpesvirus 4, Human/genetics ; Herpesvirus 4, Human/pathogenicity ; Humans ; MicroRNAs ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/genetics ; Nasopharyngeal Neoplasms/pathology ; Nasopharyngeal Neoplasms/virology ; Prognosis ; RNA, Small Untranslated
Chemical Substances	Biomarkers, Tumor ; MicroRNAs ; RNA, Small Untranslated
Language	English
Publishing date	2016-04-27
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2828547-5
ISSN	2304-3873 ; 2304-3865
ISSN (online)	2304-3873
ISSN	2304-3865
DOI	10.21037/cco.2016.03.09
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Article: HPV Associated Head and Neck Cancer.

Spence, Tara / Bruce, Jeff / Yip, Kenneth W / Liu, Fei-Fei

Cancers

2016 Volume 8, Issue 8

Abstract: Head and neck cancers (HNCs) are a highly heterogeneous group of tumours that are associated with diverse clinical outcomes. Recent evidence has demonstrated that human papillomavirus (HPV) is involved in up to 25% of HNCs; particularly in the ... ...

Abstract	Head and neck cancers (HNCs) are a highly heterogeneous group of tumours that are associated with diverse clinical outcomes. Recent evidence has demonstrated that human papillomavirus (HPV) is involved in up to 25% of HNCs; particularly in the oropharyngeal carcinoma (OPC) subtype where it can account for up to 60% of such cases. HPVs are double-stranded DNA viruses that infect epithelial cells; numerous HPV subtypes, including 16, 18, 31, 33, and 35, drive epithelial cell transformation and tumourigenesis. HPV positive (HPV+) HNC represents a distinct molecular and clinical entity from HPV negative (HPV-) disease; the biological basis for which remains to be fully elucidated. HPV positivity is strongly correlated with a significantly superior outcome; indicating that such tumours should have a distinct management approach. This review focuses on the recent scientific and clinical investigation of HPV+ HNC. In particular, we discuss the importance of molecular and clinical evidence for defining the role of HPV in HNC, and the clinical impact of HPV status as a biomarker for HNC.
Language	English
Publishing date	2016-08-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers8080075
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Article ; Online: Preclinical imaging and translational animal models of cancer for accelerated clinical implementation of nanotechnologies and macromolecular agents.

De Souza, Raquel / Spence, Tara / Huang, Huang / Allen, Christine

Journal of controlled release : official journal of the Controlled Release Society

2015 Volume 219, Page(s) 313–330

Abstract: The majority of animal models of cancer have performed poorly in terms of predicting clinical performance of new therapeutics, which are most often first evaluated in patients with advanced, metastatic disease. The development and use of metastatic ... ...

Abstract	The majority of animal models of cancer have performed poorly in terms of predicting clinical performance of new therapeutics, which are most often first evaluated in patients with advanced, metastatic disease. The development and use of metastatic models of cancer may enhance clinical translatability of preclinical studies focused on the development of nanotechnology-based drug delivery systems and macromolecular therapeutics, potentially accelerating their clinical implementation. It is recognized that the development and use of such models are not without challenge. Preclinical imaging tools offer a solution by allowing temporal and spatial characterization of metastatic lesions. This paper provides a review of imaging methods applicable for evaluation of novel therapeutics in clinically relevant models of advanced cancer. An overview of currently utilized models of oncology in small animals is followed by image-based development and characterization of visceral metastatic cancer models. Examples of imaging tools employed for metastatic lesion detection, evaluation of anti-tumor and anti-metastatic potential and biodistribution of novel therapies, as well as the co-development and/or use of imageable surrogates of response, are also discussed. While the focus is on development of macromolecular and nanotechnology-based therapeutics, examples with small molecules are included in some cases to illustrate concepts and approaches that can be applied in the assessment of nanotechnologies or macromolecules.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/therapeutic use ; Diagnostic Imaging ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Humans ; Nanotechnology ; Neoplasm Metastasis/diagnosis ; Neoplasm Metastasis/drug therapy ; Neoplasms/diagnosis ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Tissue Distribution
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2015-12-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2015.09.041
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Article: Integration of imaging into clinical practice to assess the delivery and performance of macromolecular and nanotechnology-based oncology therapies

Spence, Tara / Christine Allen / Raquel De Souza / Raymond M. Reilly / Shawn Stapleton / Yannan Dou

Journal of Controlled Release. 2015 Dec. 10, v. 219

2015

Abstract: Functional and molecular imaging has become increasingly used to evaluate interpatient and intrapatient tumor heterogeneity. Imaging allows for assessment of microenvironment parameters including tumor hypoxia, perfusion and proliferation, as well as ... ...

Abstract	Functional and molecular imaging has become increasingly used to evaluate interpatient and intrapatient tumor heterogeneity. Imaging allows for assessment of microenvironment parameters including tumor hypoxia, perfusion and proliferation, as well as tumor metabolism and the intratumoral distribution of specific molecular markers. Imaging information may be used to stratify patients for targeted therapies, and to define patient populations that may benefit from alternative therapeutic approaches. It also provides a method for non-invasive monitoring of treatment response at earlier time-points than traditional cues, such as tumor shrinkage. Further, companion diagnostic imaging techniques are becoming progressively more important for development and clinical implementation of targeted therapies. Imaging-based companion diagnostics are likely to be essential for the validation and FDA approval of targeted nanotherapies and macromolecular medicines. This review describes recent clinical advances in the use of functional and molecular imaging to evaluate the tumor microenvironment. Additionally, this article focuses on image-based assessment of distribution and anti-tumor effect of nano- and macromolecular systems.
Keywords	antineoplastic activity ; diagnostic techniques ; genetic markers ; hypoxia ; image analysis ; metabolism ; monitoring ; patients ; shrinkage
Language	English
Dates of publication	2015-1210
Size	p. 295-312.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2015.09.036
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Article ; Online: Hyperthermia-mediated drug delivery induces biological effects at the tumor and molecular levels that improve cisplatin efficacy in triple negative breast cancer.

Dunne, Michael / Dou, Yannan N / Drake, Danielle M / Spence, Tara / Gontijo, Sávio M L / Wells, Peter G / Allen, Christine

Journal of controlled release : official journal of the Controlled Release Society

2018 Volume 282, Page(s) 35–45

Abstract: Triple negative breast cancer is an aggressive disease that accounts for at least 15% of breast cancer diagnoses, and a disproportionately high percentage of breast cancer related morbidity. Intensive research efforts are focused on the development of ... ...

Abstract	Triple negative breast cancer is an aggressive disease that accounts for at least 15% of breast cancer diagnoses, and a disproportionately high percentage of breast cancer related morbidity. Intensive research efforts are focused on the development of more efficacious treatments for this disease, for which therapeutic options remain limited. The high incidence of mutations in key DNA repair pathways in triple negative breast cancer results in increased sensitivity to DNA damaging agents, such as platinum-based chemotherapies. Hyperthermia has been successfully used in breast cancer treatment to sensitize tumors to radiation therapy and chemotherapy. It has also been used as a mechanism to trigger drug release from thermosensitive liposomes. In this study, mild hyperthermia is used to trigger release of cisplatin from thermosensitive liposomes in the vasculature of human triple negative breast cancer tumors implanted orthotopically in mice. This heat-triggered liposomal formulation of cisplatin resulted in significantly delayed tumor growth and improved overall survival compared to treatment with either non-thermosensitive liposomes containing cisplatin or free cisplatin, as was observed in two independent tumor models (i.e. MDA-MB-231 and MDA-MB-436). The in vitro sensitivity of the cell lines to cisplatin and hyperthermia alone and in combination was characterized extensively using enzymatic assays, clonogenic assays, and spheroid growth assays. Evaluation of correlations between the in vitro and in vivo results served to identify the in vitro approach that is most predictive of the effects of hyperthermia in vivo. Relative expression of several heat shock proteins and the DNA damage repair protein BRCA1 were assayed at baseline and in response to hyperthermia both in vitro and in vivo. Interestingly, delivery of cisplatin in thermosensitive liposomes in combination with hyperthermia resulted in the most significant tumor growth delay, relative to free cisplatin, in the less cisplatin-sensitive cell line (i.e. MDA-MB-231). This work demonstrates that thermosensitive cisplatin liposomes used in combination with hyperthermia offer a novel method for effective treatment of triple negative breast cancer.
MeSH term(s)	Animals ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/therapeutic use ; Breast/blood supply ; Breast/drug effects ; Breast/pathology ; Cell Line, Tumor ; Cisplatin/administration & dosage ; Cisplatin/therapeutic use ; Delayed-Action Preparations/chemistry ; Drug Delivery Systems/methods ; Female ; Humans ; Hyperthermia, Induced/methods ; Liposomes/chemistry ; Mice, SCID ; Triple Negative Breast Neoplasms/blood supply ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/pathology
Chemical Substances	Antineoplastic Agents ; Delayed-Action Preparations ; Liposomes ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2018-04-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2018.04.029
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Article: Hyperthermia-mediated drug delivery induces biological effects at the tumor and molecular levels that improve cisplatin efficacy in triple negative breast cancer

Dunne, Michael / Dou, Yannan N / Drake, Danielle M / Spence, Tara / Gontijo, Sávio M.L / Wells, Peter G / Allen, Christine

Journal of controlled release. 2018 July 28, v. 282

2018

Abstract	Triple negative breast cancer is an aggressive disease that accounts for at least 15% of breast cancer diagnoses, and a disproportionately high percentage of breast cancer related morbidity. Intensive research efforts are focused on the development of more efficacious treatments for this disease, for which therapeutic options remain limited. The high incidence of mutations in key DNA repair pathways in triple negative breast cancer results in increased sensitivity to DNA damaging agents, such as platinum-based chemotherapies. Hyperthermia has been successfully used in breast cancer treatment to sensitize tumors to radiation therapy and chemotherapy. It has also been used as a mechanism to trigger drug release from thermosensitive liposomes. In this study, mild hyperthermia is used to trigger release of cisplatin from thermosensitive liposomes in the vasculature of human triple negative breast cancer tumors implanted orthotopically in mice. This heat-triggered liposomal formulation of cisplatin resulted in significantly delayed tumor growth and improved overall survival compared to treatment with either non-thermosensitive liposomes containing cisplatin or free cisplatin, as was observed in two independent tumor models (i.e. MDA-MB-231 and MDA-MB-436). The in vitro sensitivity of the cell lines to cisplatin and hyperthermia alone and in combination was characterized extensively using enzymatic assays, clonogenic assays, and spheroid growth assays. Evaluation of correlations between the in vitro and in vivo results served to identify the in vitro approach that is most predictive of the effects of hyperthermia in vivo. Relative expression of several heat shock proteins and the DNA damage repair protein BRCA1 were assayed at baseline and in response to hyperthermia both in vitro and in vivo. Interestingly, delivery of cisplatin in thermosensitive liposomes in combination with hyperthermia resulted in the most significant tumor growth delay, relative to free cisplatin, in the less cisplatin-sensitive cell line (i.e. MDA-MB-231). This work demonstrates that thermosensitive cisplatin liposomes used in combination with hyperthermia offer a novel method for effective treatment of triple negative breast cancer.
Keywords	DNA repair ; bioactive properties ; breast neoplasms ; cell lines ; cisplatin ; drug therapy ; fever ; heat shock proteins ; humans ; methodology ; mice ; models ; morbidity ; mutation ; radiotherapy ; tumor suppressor proteins
Language	English
Dates of publication	2018-0728
Size	p. 35-45.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2018.04.029
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