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Kinases as targets in the treatment of solid tumors
Authors:Georgios Giamas  Yik L Man  Heidrun Hirner  Joachim Bischof  Klaus Kramer  Kalimullah Khan  Sharmeen S Lavina Ahmed  Justin Stebbing  Uwe Knippschild
Institution:1. Department of Cancer and Surgery, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 ONN, UK;2. Department of General-, Visceral- and Transplantation Surgery, University of Ulm, Germany;1. Service d''Hématologie Clinique, Centre Hospitalier Universitaire Hôtel-Dieu, Nantes, France;2. Institut National de la Santé et de la Recherche Médicale Le Centre Régional de Recherche en Cancérologie Nantes/Angers Unité Mixte de Recherche892, Nantes, France;3. Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche938, CDR Saint-Antoine, Paris, France;4. Université Pierre et Marie Curie, Paris, France;5. Service d''Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France;1. Unit of Investigative Clinical Oncology, Piedmont Oncology Foundation, Institute for Cancer Research and Treatment, Strada Provinciale 142, Km 3.95 – 10060, Candiolo, Italy;2. Division of Medical Oncology, Piedmont Oncology Foundation, Institute for Cancer Research and Treatment, Strada Provinciale 142, Km 3.95 – 10060, Candiolo, Italy;1. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY;2. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY;3. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY;4. Department of Radiation Oncology, Mount Sinai Medical Center, New York, NY;5. Thoracic Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY;1. Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, 300 East 66th Street, Room 1033, New York, NY 10065, USA;2. Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, Room 1033, New York, NY 10065, USA;1. University of Colorado Cancer Center, Aurora, CO, USA;2. Smilow Cancer Center, Yale University, CT, USA;3. University of California Davis, CA, USA
Abstract:The protein kinase family, one of the largest gene families in eukaryotes, plays an important role in regulating various cellular processes such as cell proliferation, cell death, cell cycle progression, differentiation and cell survival. Therefore, it is not surprising that the deregulation of many kinases is usually directly linked to cancer development. In all solid tumors, changes in protein kinase expression levels and activities, as well as alterations in the degree of posttranslational modifications can contribute to cancer development. Consequently, the identification of molecular targets and signaling pathways specific to cancer cells is becoming more and more important for cancer drug development and cancer therapies. Inhibition of various protein kinases has already been investigated in many pre-clinical and clinical trials targeting all stages of signal transduction, demonstrating promising results in cancer therapy. Conventional chemotherapeutics are often ineffective as well as harmful; hence a combination of both chemotherapeutics and protein kinase inhibitors may result in new and more successful therapeutic approaches. In this review we focus on protein kinases involved in different signaling pathways and their alterations in solid tumors.
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