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Book ; Online ; E-Book: Cancer biomarkers

Ramanathan, Lakshmi V. / Fleisher, Martin / Duffy, Michael J.

clinical aspects and laboratory determination

(Clinical Aspects and Laboratory Determination Series)

2022

Author's details	edited by Lakshmi V. Ramanathan, Martin Fleisher, Michael J. Duffy
Series title	Clinical Aspects and Laboratory Determination Series
Keywords	Cancer/Diagnosis ; Tumor markers/Diagnostic use.
Subject code	616.994075
Language	English
Size	1 online resource (476 pages)
Publisher	Elsevier
Publishing place	Amsterdam, Netherlands
Document type	Book ; Online ; E-Book
Note	Description based upon print version of record.
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
ISBN	0-12-824303-1 ; 9780128243022 ; 978-0-12-824303-9 ; 0128243023
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Circulating tumor DNA (ctDNA) as a biomarker for lung cancer: Early detection, monitoring and therapy prediction.

Duffy, Michael J

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine

2023 Volume 46, Issue s1, Page(s) S283–S295

Abstract: Circulating tumor DNA (ctDNA), i.e., DNA shed from tumor cells into the bloodstream, is emerging as one of the most useful plasma biomarkers in patients with multiple types of cancer, including patients with non-small cell lung cancer (NSCLC). Indeed, ... ...

Abstract	Circulating tumor DNA (ctDNA), i.e., DNA shed from tumor cells into the bloodstream, is emerging as one of the most useful plasma biomarkers in patients with multiple types of cancer, including patients with non-small cell lung cancer (NSCLC). Indeed, NSCLC was the first malignancy in which measurement of ctDNA was approved for clinical use, i.e., mutational testing of EGFR for predicting response to EGFR tyrosine kinase inhibitors in patients with advanced disease. Although historically the gold standard method for EGFR mutational analysis required tumor tissue, the use of ctDNA is more convenient and safer for patients, results in a faster turn-around-time for return of results, provides a more complete representation of genetic alteration in heterogeneous tumors and is less costly to perform. Emerging uses of ctDNA in patients with lung or suspected lung cancer include screening for early disease, surveillance following initial treatment and monitoring response to therapy in metastatic disease. For evaluating therapy response, ctDNA appears to be especially useful in patients receiving targeted therapies against driver oncogenes or immunotherapy. Further work should not only validate these emerging findings but also aim to optimize and standardize ctDNA assays.
MeSH term(s)	Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/genetics ; Lung Neoplasms/drug therapy ; Carcinoma, Non-Small-Cell Lung/diagnosis ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Circulating Tumor DNA/genetics ; ErbB Receptors/genetics ; Mutation ; Biomarkers, Tumor/genetics
Chemical Substances	Circulating Tumor DNA ; ErbB Receptors (EC 2.7.10.1) ; Biomarkers, Tumor
Language	English
Publishing date	2023-06-02
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	605825-5
ISSN	1423-0380 ; 0289-5447 ; 1010-4283
ISSN (online)	1423-0380
ISSN	0289-5447 ; 1010-4283
DOI	10.3233/TUB-220044
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Zs.A 1598: Show issues

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Article ; Online: Circulating tumor DNA (ctDNA): can it be used as a pan-cancer early detection test?

Duffy, Michael J / Crown, John

Critical reviews in clinical laboratory sciences

2023 , Page(s) 1–13

Abstract: Circulating tumor DNA (ctDNA, DNA shed by cancer cells) is emerging as one of the most transformative cancer biomarkers discovered to-date. Although potentially useful at all the phases of cancer detection and patient management, one of its most exciting ...

Abstract	Circulating tumor DNA (ctDNA, DNA shed by cancer cells) is emerging as one of the most transformative cancer biomarkers discovered to-date. Although potentially useful at all the phases of cancer detection and patient management, one of its most exciting possibilities is as a relatively noninvasive pan-cancer screening test. Preliminary findings with ctDNA tests such as Galleri or CancerSEEK suggest that they have high specificity (> 99.0%) for malignancy. Their sensitivity varies depending on the type of cancer and stage of disease but it is generally low in patients with stage I disease. A major advantage of ctDNA over existing screening strategies is the potential ability to detect multiple cancer types in a single test. A limitation of most studies published to-date is that they are predominantly case-control investigations that were carried out in patients with a previous diagnosis of malignancy and that used apparently healthy subjects as controls. Consequently, the reported sensitivities, specificities and positive predictive values might be lower if the tests are used for screening in asymptomatic populations, that is, in the population where these tests are likely be employed. To demonstrate clinical utility in an asymptomatic population, these tests must be shown to reduce cancer mortality without causing excessive overdiagnosis in a large randomized prospective randomized trial. Such trials are currently ongoing for Galleri and CancerSEEK.
Language	English
Publishing date	2023-11-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	280641-1
ISSN	1549-781X ; 1040-8363 ; 0590-8191
ISSN (online)	1549-781X
ISSN	1040-8363 ; 0590-8191
DOI	10.1080/10408363.2023.2275150
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Article: Use of Circulating Tumour DNA (ctDNA) for Measurement of Therapy Predictive Biomarkers in Patients with Cancer.

Duffy, Michael J / Crown, John

Journal of personalized medicine

2022 Volume 12, Issue 1

Abstract: Biomarkers that predict likely response or resistance to specific therapies are critical in personalising treatment for cancer patients. Such biomarkers are now available for an increasing number of anti-cancer therapies, especially targeted therapy and ... ...

Abstract	Biomarkers that predict likely response or resistance to specific therapies are critical in personalising treatment for cancer patients. Such biomarkers are now available for an increasing number of anti-cancer therapies, especially targeted therapy and immunotherapy. The gold-standard method for determining predictive biomarkers requires tumour tissue. Obtaining tissue, however, is not always possible and even if possible, the amount or quality of tissue obtained may be inadequate for biomarker analysis. Tumour DNA, however, can be released into the bloodstream, giving rise to what is referred to as circulating tumour DNA (ctDNA). In contrast to tissue, blood can be obtained from effectively all patients in a minimally invasive and safe manner. Other advantages of blood over tissue for biomarker testing include a shorter turn-around time and an ability to perform serial measurements. Furthermore, blood should provide a more complete profile of mutations present in heterogeneous tumours than a single-needle tissue biopsy. A limitation of blood vis-à-vis tissue, however, is lower sensitivity and, thus, the possibility of missing an actionable mutation. Despite this limitation, blood-based predictive biomarkers, such as mutant
Language	English
Publishing date	2022-01-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm12010099
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Article ; Online: Circulating Tumor DNA as a Biomarker for Monitoring Patients with Solid Cancers: Comparison with Standard Protein Biomarkers.

Duffy, Michael J / Crown, John

Clinical chemistry

2022 Volume 68, Issue 11, Page(s) 1381–1390

Abstract: Background: Protein-based biomarkers are widely used in monitoring patients with diagnosed cancer. These biomarkers however, lack specificity for cancer and have poor sensitivity in detecting early recurrences and monitoring therapy effectiveness. ... ...

Abstract	Background: Protein-based biomarkers are widely used in monitoring patients with diagnosed cancer. These biomarkers however, lack specificity for cancer and have poor sensitivity in detecting early recurrences and monitoring therapy effectiveness. Emerging data suggest that the use of circulating tumor DNA (ctDNA) has several advantages over standard biomarkers. Content: Following curative-intent surgery for cancer, the presence of ctDNA is highly predictive of early disease recurrence, while in metastatic cancer an early decline in ctDNA following the initiation of treatment is predictive of good outcome. Compared with protein biomarkers, ctDNA provides greater cancer specificity and sensitivity for detecting early recurrent/metastatic disease. Thus, in patients with surgically resected colorectal cancer, multiple studies have shown that ctDNA is superior to carcinoembryonic antigen (CEA) in detecting residual disease and early recurrence. Similarly, in breast cancer, ctDNA was shown to be more accurate than carbohydrate antigen 15-3 (CA 15-3) in detecting early recurrences. Other advantages of ctDNA over protein biomarkers in monitoring cancer patients include a shorter half-life in plasma and an ability to predict likely response to specific therapies and identify mechanisms of therapy resistance. However, in contrast to proteins, ctDNA biomarkers are more expensive to measure, less widely available, and have longer turnaround times for reporting. Furthermore, ctDNA assays are less well standardized. Summary: Because of their advantages, it is likely that ctDNA measurements will enter clinical use in the future, where they will complement existing biomarkers and imaging in managing patients with cancer. Hopefully, these combined approaches will lead to a better outcome for patients.
MeSH term(s)	Humans ; Female ; Circulating Tumor DNA ; Biomarkers, Tumor ; Neoplasm Recurrence, Local/genetics ; Breast Neoplasms
Chemical Substances	Circulating Tumor DNA ; Biomarkers, Tumor
Language	English
Publishing date	2022-08-12
Publishing country	England
Document type	Journal Article
ZDB-ID	80102-1
ISSN	1530-8561 ; 0009-9147
ISSN (online)	1530-8561
ISSN	0009-9147
DOI	10.1093/clinchem/hvac121
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Article ; Online: Biomarkers for prostate cancer: prostate-specific antigen and beyond.

Duffy, Michael J

Clinical chemistry and laboratory medicine

2019 Volume 58, Issue 3, Page(s) 326–339

Abstract: In recent years, several new biomarkers supplementing the role of prostate-specific antigen (PSA) have become available for men with prostate cancer. Although widely used in an ad hoc manner, the role of PSA in screening asymptomatic men for prostate ... ...

Abstract	In recent years, several new biomarkers supplementing the role of prostate-specific antigen (PSA) have become available for men with prostate cancer. Although widely used in an ad hoc manner, the role of PSA in screening asymptomatic men for prostate cancer is controversial. Several expert panels, however, have recently recommended limited PSA screening following informed consent in average-risk men, aged 55-69 years. As a screening test for prostate cancer however, PSA has limited specificity and leads to overdiagnosis which in turn results in overtreatment. To increase specificity and reduce the number of unnecessary biopsies, biomarkers such as percent free PSA, prostate health index (PHI) or the 4K score may be used, while Progensa PCA3 may be measured to reduce the number of repeat biopsies in men with a previously negative biopsy. In addition to its role in screening, PSA is also widely used in the management of patients with diagnosed prostate cancer such as in surveillance following diagnosis, monitoring response to therapy and in combination with both clinical and histological criteria in risk stratification for recurrence. For determining aggressiveness and predicting outcome, especially in low- or intermediate-risk men, tissue-based multigene tests such as Decipher, Oncotype DX (Prostate), Prolaris and ProMark, may be used. Emerging therapy predictive biomarkers include AR-V7 for predicting lack of response to specific anti-androgens (enzalutamide, abiraterone), BRAC1/2 mutations for predicting benefit from PARP inhibitor and PORTOS for predicting benefit from radiotherapy. With the increased availability of multiple biomarkers, personalised treatment for men with prostate cancer is finally on the horizon.
MeSH term(s)	Biomarkers, Tumor/blood ; Humans ; Male ; Mass Screening ; Prognosis ; Prostate-Specific Antigen/blood ; Prostatic Neoplasms/blood ; Prostatic Neoplasms/diagnosis ; Risk Assessment
Chemical Substances	Biomarkers, Tumor ; Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2019-11-10
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1418007-8
ISSN	1437-4331 ; 1434-6621 ; 1437-8523
ISSN (online)	1437-4331
ISSN	1434-6621 ; 1437-8523
DOI	10.1515/cclm-2019-0693
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Article ; Online: Degradation of MYC by the mutant p53 reactivator drug, COTI-2 in breast cancer cells.

Tang, Minhong / Crown, John / Duffy, Michael J

Investigational new drugs

2023 Volume 41, Issue 4, Page(s) 541–550

Abstract: TP53 (p53) and MYC are amongst the most frequently altered genes in cancer. Both are thus attractive targets for new anticancer therapies. Historically, however, both genes have proved challenging to target and currently there is no approved therapy ... ...

Abstract	TP53 (p53) and MYC are amongst the most frequently altered genes in cancer. Both are thus attractive targets for new anticancer therapies. Historically, however, both genes have proved challenging to target and currently there is no approved therapy against either. The aim of this study was to investigate the effect of the mutant p53 reactivating drug, COTI-2 on MYC. Total MYC, pSer62 MYC and pThr58 MYC were detected using Western blotting. Proteasome-mediated degradation was determined using the proteasome, inhibitor MG-132, while MYC half-life was measured using pulse chase experiments in the presence of cycloheximide. Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Treatment of 5 mutant p53 breast cancer cell lines with COTI-2 resulted in dose-dependent MYC degradation. Addition of the proteasome inhibitor, MG132, rescued the degradation, suggesting that this proteolytic system was at least partly responsible for the inactivation of MYC. Using cycloheximide in pulse chase experiments, COTI-2 was found to reduce the half-life of MYC in 2 different mutant p53 breast cancer cell lines, i.e., from 34.8 to 18.6 min in MDA-MB-232 cells and from 29.6 to 20.3 min in MDA-MB-468 cells. Co-treatment with COTI-2 and the MYC inhibitor, MYCi975 resulted in synergistic growth inhibition in all 4 mutant p53 cell lines investigated. The dual ability of COTI-2 to reactivate mutant p53 and degrade MYC should enable this compound to have broad application as an anticancer drug.
MeSH term(s)	Female ; Humans ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Apoptosis ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Cell Line, Tumor ; Cell Proliferation ; Cycloheximide/pharmacology ; Proteasome Endopeptidase Complex/metabolism ; Proteasome Endopeptidase Complex/pharmacology ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Antineoplastic Agents ; Cycloheximide (98600C0908) ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Tumor Suppressor Protein p53 ; COTI-2 compound
Language	English
Publishing date	2023-05-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604895-x
ISSN	1573-0646 ; 0167-6997
ISSN (online)	1573-0646
ISSN	0167-6997
DOI	10.1007/s10637-023-01368-1
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Article ; Online: Living with loss: a cognitive approach to prolonged grief disorder - incorporating complicated, enduring and traumatic grief.

Duffy, Michael / Wild, Jennifer

Behavioural and cognitive psychotherapy

2023 Volume 51, Issue 6, Page(s) 645–658

MeSH term(s)	Humans ; Prolonged Grief Disorder ; Grief ; Stress Disorders, Post-Traumatic/therapy ; Stress Disorders, Post-Traumatic/psychology ; Cognitive Behavioral Therapy ; Cognition ; Bereavement
Language	English
Publishing date	2023-05-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	1168441-0
ISSN	1469-1833 ; 1352-4658 ; 0141-3473
ISSN (online)	1469-1833
ISSN	1352-4658 ; 0141-3473
DOI	10.1017/S1352465822000674
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Article ; Online: Living with loss: a cognitive approach to prolonged grief disorder - incorporating complicated, enduring and traumatic grief - ADDENDUM.

Duffy, Michael / Wild, Jennifer

Behavioural and cognitive psychotherapy

2023 Volume 51, Issue 6, Page(s) 660

Abstract: The subject of prolonged, complicated and traumatic grief has become more topical as a consequence of the Covid-19 pandemic. CBT practitioners have been asked to provide effective therapeutic responses for clients with enduring distressing grief ... ...

Abstract	The subject of prolonged, complicated and traumatic grief has become more topical as a consequence of the Covid-19 pandemic. CBT practitioners have been asked to provide effective therapeutic responses for clients with enduring distressing grief reactions. These enduring grief conditions have now been categorised as Prolonged Grief Disorder in the two main mental health classification systems: in the ICD -11 in November 2020 and as a revision to the DSM-5 in 2021. In this paper we draw on our research and clinical experience in applying cognitive therapy for PTSD (CT-PTSD) to traumatic bereavement to derive lessons for the treatment of prolonged grief. During the pandemic the authors of this paper delivered several workshops on prolonged grief disorder (PGD) during which clinicians raised several thought-provoking questions; how do we differentiate between normal and abnormal or pathological grief; how do we categorise pathological grief; how effective are existing therapies and is there a role for CBT; and how do our experiences with Cognitive Therapy for PTSD help with conceptualisation and treatment of PGD. The purpose of this paper is to answer these important questions and in so doing, consider the historical and theoretical concepts relating to complex and traumatic grief, factors that differentiate normal grief from abnormal grief, maintenance factors for PGD and implications for CBT treatments.
MeSH term(s)	Humans ; Prolonged Grief Disorder ; Pandemics ; Bereavement ; Grief ; Cognitive Behavioral Therapy ; Cognition ; Stress Disorders, Post-Traumatic/therapy ; Stress Disorders, Post-Traumatic/psychology
Language	English
Publishing date	2023-06-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	1168441-0
ISSN	1469-1833 ; 1352-4658 ; 0141-3473
ISSN (online)	1469-1833
ISSN	1352-4658 ; 0141-3473
DOI	10.1017/S1352465823000279
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Article ; Online: Incidence of quadricuspid pulmonary valves at postmortem examination.

Duffy, Michael / Parsons, Sarah / Westaby, Joseph / Sheppard, Mary

Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology

2024 Volume 71, Page(s) 107636

Abstract: Quadricuspid pulmonic valve is a rare congenital abnormality and because of its difficult non-invasive assessment, it is usually discovered incidentally at autopsies (reported prevalence in post-mortem specimens ranges from 1 in 400 to 1 in 2000). Unlike ...

Abstract	Quadricuspid pulmonic valve is a rare congenital abnormality and because of its difficult non-invasive assessment, it is usually discovered incidentally at autopsies (reported prevalence in post-mortem specimens ranges from 1 in 400 to 1 in 2000). Unlike a bicuspid pulmonary valve, it rarely presents with clinical complications, such as valvular insufficiency or stenosis. Abnormal function is rarely reported in cases that are not associated with other congenital heart disease. With increased sophistication of imaging coincidental quadricuspid valves autopsy studies are important to understand the anatomical consequences of this finding. Our case series identified 21 QPV cases from the Victorian Institute of Forensic Medicine, Melbourne and St George's University of London, Department of Cardiovascular Pathology. Cases were identified through local database searches and review of autopsy/cardiac examination reports over a 20-year period. Available photographs were also systematically examined. Fifteen cases had causes of death with no direct causality to cardiac valvular pathology alone. Six cases were considered unascertained or similar (sudden arrhythmic death syndrome and sudden unexpected death in epilepsy). The presence of QPV in these instances were uncertain but thought to be unlikely contributory to death, due to the absence of pulmonary valvular complications.
Language	English
Publishing date	2024-03-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	1134600-0
ISSN	1879-1336 ; 1054-8807
ISSN (online)	1879-1336
ISSN	1054-8807
DOI	10.1016/j.carpath.2024.107636
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