Cited by 1,070Cancer Genomics and DiagnosticsLung Cancer Treatments and MutationsCancer Immunotherapy and Biomarkers

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Combinatorial drug therapy for cancer in the post-genomic era

Al-Lazikani, Bissan, Banerji, Udai, Workman, Paul·2012·Nature Biotechnology

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Abstract

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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A Diverse Stochastic Search Algorithm for Combination Therapeutics
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Background

Authors: Al-Lazikani, B., Banerji, U., & Workman, P.
Affiliations: Royal Marsden NHS Foundation Trust (GB)
Institute of Cancer Research (GB)
Corresponding author: Banerji, Udai
Workman, Paul
ORCID: Banerji, Udai
Workman, Paul
Venue: Nature Biotechnology
Publisher: Springer Science and Business Media LLC
Published: 2012-07
Volume: 30
Issue: 7
Pages: 679-692
ISSN: 0733-222X (ISSN-L)
1087-0156
1546-1696
DOI: 10.1038/nbt.2284
OpenAlex: W2061061337
Cited by: 1,070
References: 172
Citations by year: 2026: 63 · 2025: 80 · 2024: 71 · 2023: 73 · 2022: 87 · 2021: 73 · 2020: 80 · 2019: 91 · 2018: 81 · 2017: 76 · 2016: 83 · 2015: 90 · 2014: 69 · 2013: 46 · 2012: 6
FWCI: 5.04
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Biotechnology (publishedVersion)
PubMed (publishedVersion)
Funders: NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
Cancer Research UK (C309/8992, 11566, C309/A8274)
National Institute for Health and Care Research
National Institutes of Health
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords: combination therapy, targeted cancer therapy, driver mutations, synthetic lethality, tumor vulnerability, precision oncology, acquired drug resistance, de novo resistance, polygenic resistance, cytotoxic chemotherapy
MeSH terms: Antineoplastic Combined Chemotherapy Protocols, Clinical Trials as Topic, Combined Modality Therapy, Humans, Neoplasms, Drug Design, Genome, Human, Genetic Heterogeneity, Metabolic Networks and Pathways, Precision Medicine, Molecular Targeted Therapy, High-Throughput Nucleotide Sequencing

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Combinatorial drug therapy for cancer in the post-genomic era

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