Abstract
KRAS proteins play a major role in human cancer, but have not yielded to therapeutic attack. New technologies in drug discovery and insights into signaling pathways that KRAS controls have promoted renewed efforts to develop therapies through direct targeting of KRAS itself, new ways of blocking KRAS processing, or by identifying targets that KRAS cancers depend on for survival. Although drugs that block the well-established downstream pathways, RAF-MAPK and PI3K, are being tested in the clinic, new efforts are under way to exploit previously unrecognized vulnerabilities, such as altered metabolic networks, or novel pathways identified through synthetic lethal screens. Furthermore, new ways of suppressing KRAS gene expression and of harnessing the immune system offer further hope that new ways of treating KRAS are finally coming into view. These issues are discussed in this edition of CCR Focus.
©2015 American Association for Cancer Research.
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism
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Drug Resistance, Neoplasm / genetics
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Genetic Therapy
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Humans
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Immunity / genetics
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Immunotherapy
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Molecular Targeted Therapy*
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Mutation
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Neoplasms / genetics
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Neoplasms / immunology
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Neoplasms / metabolism*
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Neoplasms / therapy*
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use
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Protein Subunits / antagonists & inhibitors
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Protein Subunits / genetics
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Protein Subunits / metabolism
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Proto-Oncogene Proteins p21(ras) / antagonists & inhibitors*
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Proto-Oncogene Proteins p21(ras) / chemistry
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Proto-Oncogene Proteins p21(ras) / genetics
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Proto-Oncogene Proteins p21(ras) / metabolism*
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RNA Interference
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RNA, Small Interfering / genetics
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Signal Transduction / drug effects
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Protein Subunits
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RNA, Small Interfering
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Proto-Oncogene Proteins p21(ras)