TY - JOUR
T1 - Genome-based cancer therapeutics
T2 - Targets, kinase drug resistance and future strategies for precision oncology
AU - Workman, Paul
AU - Al-Lazikani, Bissan
AU - Clarke, Paul A.
N1 - Funding Information:
PAC, BA-L and PW are grateful for major core support from Cancer Research UK (programme grant C309/A8725 ). PW is a Cancer Research UK Life Fellow. The authors acknowledge funding to The Institute of Cancer Research and the Royal Marsden Hospital as a Cancer Research UK Centre and from the National Institute of Health Research to our Biomedical Research Centre. We apologize to the authors of numerous excellent papers that could not be cited because of space constraints. We thank our many colleagues, collaborators and laboratory staff for valuable discussions. We thank Val Cornwell for excellent administrative support.
PY - 2013
Y1 - 2013
N2 - Extraordinary progress has been made in our detailed understanding of the genetic and epigenetic mechanisms responsible for oncogenesis and cancer progression. Empowered by next-generation sequencing, many new targets and pathways have been identified to exploit oncogene and non-oncogene addiction and synthetic lethality. Kinase inhibitors feature strongly in the druggable cancer genome and 19 have been approved in oncology. While survival gains are valuable, drug resistance has emerged as the major challenge. The clonal heterogeneity and evolution of cancers is an intrinsic problem, together with feedback loops, kinase switching and activation of alternative targets and pathways. The solution to drug resistance will require the use of rationally targeted combinational regimens. The application of adaptive treatment cycles based on ongoing multi-technology profiling will be the key to long-term therapeutic success.
AB - Extraordinary progress has been made in our detailed understanding of the genetic and epigenetic mechanisms responsible for oncogenesis and cancer progression. Empowered by next-generation sequencing, many new targets and pathways have been identified to exploit oncogene and non-oncogene addiction and synthetic lethality. Kinase inhibitors feature strongly in the druggable cancer genome and 19 have been approved in oncology. While survival gains are valuable, drug resistance has emerged as the major challenge. The clonal heterogeneity and evolution of cancers is an intrinsic problem, together with feedback loops, kinase switching and activation of alternative targets and pathways. The solution to drug resistance will require the use of rationally targeted combinational regimens. The application of adaptive treatment cycles based on ongoing multi-technology profiling will be the key to long-term therapeutic success.
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U2 - 10.1016/j.coph.2013.06.004
DO - 10.1016/j.coph.2013.06.004
M3 - Review article
C2 - 23810823
AN - SCOPUS:84885957225
SN - 1471-4892
VL - 13
SP - 486
EP - 496
JO - Current Opinion in Pharmacology
JF - Current Opinion in Pharmacology
IS - 4
ER -