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dc.contributor.authorDean, Emma J
dc.contributor.authorGreystoke, Alastair
dc.contributor.authorRanson, Malcolm R
dc.contributor.authorDive, Caroline
dc.date.accessioned2012-08-29T16:15:38Z
dc.date.available2012-08-29T16:15:38Z
dc.date.issued2012-07-01
dc.identifier.citationBiomarkers of cell death applicable to early clinical trials. 2012, 318 (11):1252-9 Exp Cell Resen_GB
dc.identifier.issn1090-2422
dc.identifier.pmid22483936
dc.identifier.doi10.1016/j.yexcr.2012.03.020
dc.identifier.urihttp://hdl.handle.net/10541/240460
dc.description.abstractThe development of biomarkers of cell death to reflect tumor biology and drug-induced response has garnered interest with the development of several classes of drugs aimed at decreasing the cellular threshold for apoptosis and exploiting pre-existing oncogenic stresses. These novel anticancer drugs, directly targeted to the apoptosis regulatory machinery and aimed at abrogating survival signaling pathways, are entering early clinical trials provoking the question of how to monitor their impact on cancer patients. The parallel development of drugs with predictive biomarkers and their incorporation into early clinical trials are anticipated to support the pharmacological audit trail, to speed the development and reduce the attrition rate of novel drugs whose objective is to provoke tumor cell death. Tumor biopsies are an ideal matrix to measure apoptosis, but surrogate less invasive biomarkers such as blood samples and functional imaging are less challenging to acquire clinically. Archetypal and exploratory examples illustrating the importance of biomarkers to drug development are given. This review explores the substantive challenges associated with the validation, deployment, interpretation and utility of biomarkers of cell death and reviews recent advances in their incorporation in preclinical and early clinical trial contexts.
dc.language.isoenen
dc.rightsArchived with thanks to Experimental cell researchen_GB
dc.titleBiomarkers of cell death applicable to early clinical trials.en
dc.typeArticleen
dc.contributor.departmentPaterson Institute for Cancer Research, The University of Manchester, Withington, Manchester, UK. edean@picr.man.ac.uken_GB
dc.identifier.journalExperimental Cell Researchen_GB
html.description.abstractThe development of biomarkers of cell death to reflect tumor biology and drug-induced response has garnered interest with the development of several classes of drugs aimed at decreasing the cellular threshold for apoptosis and exploiting pre-existing oncogenic stresses. These novel anticancer drugs, directly targeted to the apoptosis regulatory machinery and aimed at abrogating survival signaling pathways, are entering early clinical trials provoking the question of how to monitor their impact on cancer patients. The parallel development of drugs with predictive biomarkers and their incorporation into early clinical trials are anticipated to support the pharmacological audit trail, to speed the development and reduce the attrition rate of novel drugs whose objective is to provoke tumor cell death. Tumor biopsies are an ideal matrix to measure apoptosis, but surrogate less invasive biomarkers such as blood samples and functional imaging are less challenging to acquire clinically. Archetypal and exploratory examples illustrating the importance of biomarkers to drug development are given. This review explores the substantive challenges associated with the validation, deployment, interpretation and utility of biomarkers of cell death and reviews recent advances in their incorporation in preclinical and early clinical trial contexts.


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