TY - JOUR
T1 - Predictive biomarkers for personalised anti-cancer drug use
T2 - Discovery to clinical implementation
AU - Alymani, Nayef A.
AU - Smith, Murray D.
AU - Williams, David J.
AU - Petty, Russell D.
N1 - Funding Information:
The authors are active in biomarker research in Oesophagogastric, Lung and Colorectal cancer work funded by NHS Grampian , Friends of the Aberdeen North Haematology, Oncology and Radiotherapy , Aberdeen Royal Infirmary Oncology Research Fund , and the Saudi Arabian Department of Cultural Affairs .
PY - 2010/3/1
Y1 - 2010/3/1
N2 - A priority translational research objective in cancer medicine is the discovery of novel therapeutic targets for solid tumours. Ideally, co-discovery of predictive biomarkers occurs in parallel to facilitate clinical development of agents and ultimately personalise clinical use. However, the identification of clinically useful predictive biomarkers for solid tumours has proven challenging with many initially promising biomarkers failing to translate into clinically useful applications. In particular, the 'failure' of a predictive biomarker has often only become apparent at a relatively late stage in investigation. Recently, the field has recognised the need to develop a robust clinical biomarker development methodology to facilitate the process. This review discusses the recent progress in this area focusing on the key stages in the biomarker development process: discovery, validation, qualification and implementation. Concentrating on predictive biomarkers for selecting systemic therapies for individual patients in the clinic, the advances and progress in each of these stages in biomarker development are outlined and the key remaining challenges are discussed. Specific examples are discussed to illustrate the challenges identified and how they have been addressed. Overall, we find that significant progress has been made towards a formalised biomarker developmental process. This holds considerable promise for facilitating the translation of predictive biomarkers from discovery to clinical implementation. Further enhancements could eventually be found through alignment with regulatory processes.
AB - A priority translational research objective in cancer medicine is the discovery of novel therapeutic targets for solid tumours. Ideally, co-discovery of predictive biomarkers occurs in parallel to facilitate clinical development of agents and ultimately personalise clinical use. However, the identification of clinically useful predictive biomarkers for solid tumours has proven challenging with many initially promising biomarkers failing to translate into clinically useful applications. In particular, the 'failure' of a predictive biomarker has often only become apparent at a relatively late stage in investigation. Recently, the field has recognised the need to develop a robust clinical biomarker development methodology to facilitate the process. This review discusses the recent progress in this area focusing on the key stages in the biomarker development process: discovery, validation, qualification and implementation. Concentrating on predictive biomarkers for selecting systemic therapies for individual patients in the clinic, the advances and progress in each of these stages in biomarker development are outlined and the key remaining challenges are discussed. Specific examples are discussed to illustrate the challenges identified and how they have been addressed. Overall, we find that significant progress has been made towards a formalised biomarker developmental process. This holds considerable promise for facilitating the translation of predictive biomarkers from discovery to clinical implementation. Further enhancements could eventually be found through alignment with regulatory processes.
KW - Anti-cancer agents
KW - Biomarkers
KW - Personalised therapy
KW - Targeted Agents
KW - Drug Discovery/methods
KW - Reproducibility of Results
KW - Humans
KW - Antineoplastic Agents/therapeutic use
KW - Neoplasms/drug therapy
KW - Biomarkers, Tumor
KW - Translational Research, Biomedical/methods
KW - Drug Screening Assays, Antitumor/methods
KW - Clinical Trials as Topic/methods
KW - Precision Medicine
UR - http://www.scopus.com/inward/record.url?scp=77649190855&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2010.01.001
DO - 10.1016/j.ejca.2010.01.001
M3 - Review article
C2 - 20138504
AN - SCOPUS:77649190855
SN - 0959-8049
VL - 46
SP - 869
EP - 879
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 5
ER -