AffiliationPaterson Institute for Cancer Research, The University of Manchester, Withington, Manchester, UK. firstname.lastname@example.org
MetadataShow full item record
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.
CitationBiomarkers of cell death applicable to early clinical trials. 2012, 318 (11):1252-9 Exp Cell Res
JournalExperimental Cell Research
- Parallel anticancer drug development and molecular stratification to qualify predictive biomarkers: dealing with obstacles hindering progress.
- Authors: Garcia VM, Cassier PA, de Bono J
- Issue date: 2011 Aug
- Pharmacodynamic biomarkers for molecular cancer therapeutics.
- Authors: Sarker D, Workman P
- Issue date: 2007
- From darkness to light with biomarkers in early clinical trials of cancer drugs.
- Authors: Carden CP, Banerji U, Kaye SB, Workman P, de Bono JS
- Issue date: 2009 Feb
- Biomarker-driven early clinical trials in oncology: a paradigm shift in drug development.
- Authors: Tan DS, Thomas GV, Garrett MD, Banerji U, de Bono JS, Kaye SB, Workman P
- Issue date: 2009 Sep-Oct
- Biomarkers of breast cancer apoptosis induced by chemotherapy and TRAIL.
- Authors: Leong S, McKay MJ, Christopherson RI, Baxter RC
- Issue date: 2012 Feb 3