Molecular chess? Hallmarks of anti-cancer drug resistance

BMC Cancer

Review

Ian A. Cree¹  Peter Charlton² 

[1] Department of Pathology, University Hospitals Coventry and Warwickshire, CV2 2DX, Coventry, UK;Faculty of Health and Life Sciences, Coventry University, Priory Street, CV1 5FB, Coventry, UK;Imperial Innovations, 52 Princes Gate, Exhibition Road, SW7 2PG, London, UK;

关键词: Cancer;    Chemotherapy;    Resistance;    Tyrosine kinase inhibitor;    Apoptosis;    Proliferation;    DNA damage;    Detoxification;    Microenvironment;    Heterogeneity;   

DOI  :  10.1186/s12885-016-2999-1

 received in 2016-08-25, accepted in 2016-12-13,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe development of resistance is a problem shared by both classical chemotherapy and targeted therapy. Patients may respond well at first, but relapse is inevitable for many cancer patients, despite many improvements in drugs and their use over the last 40 years.ReviewResistance to anti-cancer drugs can be acquired by several mechanisms within neoplastic cells, defined as (1) alteration of drug targets, (2) expression of drug pumps, (3) expression of detoxification mechanisms, (4) reduced susceptibility to apoptosis, (5) increased ability to repair DNA damage, and (6) altered proliferation. It is clear, however, that changes in stroma and tumour microenvironment, and local immunity can also contribute to the development of resistance. Cancer cells can and do use several of these mechanisms at one time, and there is considerable heterogeneity between tumours, necessitating an individualised approach to cancer treatment. As tumours are heterogeneous, positive selection of a drug-resistant population could help drive resistance, although acquired resistance cannot simply be viewed as overgrowth of a resistant cancer cell population. The development of such resistance mechanisms can be predicted from pre-existing genomic and proteomic profiles, and there are increasingly sophisticated methods to measure and then tackle these mechanisms in patients.ConclusionThe oncologist is now required to be at least one step ahead of the cancer, a process that can be likened to ‘molecular chess’. Thus, as well as an increasing role for predictive biomarkers to clinically stratify patients, it is becoming clear that personalised strategies are required to obtain best results.

【 授权许可】

CC BY   
© The Author(s). 2017