Combinatorial drug therapy for cancer in the post-genomic era.
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Over the past decade, whole genome sequencing and other 'omics' technologies have defined pathogenic driver mutations to which tumor cells are addicted. Such addictions, synthetic lethalities and other tumor vulnerabilities have yielded novel targets for a new generation of cancer drugs to treat discrete, genetically defined patient subgroups. This personalized cancer medicine strategy could eventually replace the conventional one-size-fits-all cytotoxic chemotherapy approach. However, the extraordinary intratumor genetic heterogeneity in cancers revealed by deep sequencing explains why de novo and acquired resistance arise with molecularly targeted drugs and cytotoxic chemotherapy, limiting their utility. One solution to the enduring challenge of polygenic cancer drug resistance is rational combinatorial targeted therapy.
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Antineoplastic Combined Chemotherapy Protocols
Combined Modality Therapy
Metabolic Networks and Pathways
Clinical Trials as Topic
Molecular Targeted Therapy
High-Throughput Nucleotide Sequencing
Computational Biology and Chemogenomics
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
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Nature biotechnology, 2012, 30 (7), pp. 679 - 692