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Cancers 2018, 10(6), 155; https://doi.org/10.3390/cancers10060155

Targeted Tumor Therapy Remixed—An Update on the Use of Small-Molecule Drugs in Combination Therapies

Department of Dermatology and Allergic Diseases, University of Ulm, 89081 Ulm, Germany
Received: 23 April 2018 / Revised: 18 May 2018 / Accepted: 22 May 2018 / Published: 24 May 2018
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Abstract

Over the last decade, the treatment of tumor patients has been revolutionized by the highly successful introduction of novel targeted therapies, in particular small-molecule kinase inhibitors and monoclonal antibodies, as well as by immunotherapies. Depending on the mutational status, BRAF and MEK inhibitor combinations or immune checkpoint inhibitors are current first-line treatments for metastatic melanoma. However, despite great improvements of survival rates limitations due to tumor heterogeneity, primary and acquired therapy resistance, immune evasion, and economical considerations will need to be overcome. Accordingly, ongoing clinical trials explore the individualized use of small-molecule drugs in new targeted therapy combinations based on patient parameters and tumor biopsies. With focus on melanoma therapy this review aims at providing a comprehensive overview of such novel alternative and combinational therapy strategies currently emerging from basic research. The molecular principles and drug classes that may hold promise for improved tumor therapy combination regimens including kinase inhibition, induction of apoptosis, DNA-damage response inhibition, epigenetic reprogramming, telomerase inhibition, redox modulation, metabolic reprogramming, proteasome inhibition, cancer stem cell transdifferentiation, immune cell signaling modulation, and others, are explained in brief. In addition, relevant targeted therapy combinations in current clinical trials and individualized treatment strategies are highlighted. View Full-Text
Keywords: apoptosis; clinical trial; DNA-damage response; epigenetics; kinase inhibitor; melanoma; metabolomics; small-molecule; targeted therapy; tumor apoptosis; clinical trial; DNA-damage response; epigenetics; kinase inhibitor; melanoma; metabolomics; small-molecule; targeted therapy; tumor
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Gatzka, M.V. Targeted Tumor Therapy Remixed—An Update on the Use of Small-Molecule Drugs in Combination Therapies. Cancers 2018, 10, 155.

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