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Exploiting Kinase Inhibitors for Cancer Treatment: An Overview of Clinical Results and Outlook

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Proteinkinase Inhibitors

Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 36))

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Abstract

Mutated or dysregulated protein kinases represent major oncogenic drivers in cancer. Due to the general druggability of these potential oncoproteins, protein kinases have been regarded the most significant drug targets in cancer cells for the past three decades. Starting with the approval of imatinib for targeting BCR-ABL in leukemia positive for Philadelphia chromosome, a multitude of different kinase inhibitors have been developed and approved for the market so far. Additionally, many new compounds with increased efficacy and target specificity are under development and clinical testing. While several of these compounds allow for an efficient temporary treatment success in different tumor entities, long-term cancer control is often limited due to the development of therapy resistance. Thus, overcoming drug resistance in tumors represents a major challenge for successful cancer therapies in the future.

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Abbreviations

ALL:

Acute lymphoblastic leukemia

CEL:

Chronic eosinophilic leukemia

CLL:

Chronic lymphoblastic leukemia

CML:

Chronic myeloid leukemia

CNS:

Central nervous system

CRC:

Colorectal cancer

DFSP:

Dermatofibrosarcoma protuberans

ER:

Estrogen receptor

FDA:

Food and Drug Administration

GI:

Gastrointestinal

GIST:

Gastrointestinal stromal tumor

HCC:

Hepatocellular carcinoma

HES:

Hypereosinophilic syndrome

MDS/MDP:

Myelodysplastic/myeloproliferative diseases

NRY:

Non-receptor protein-tyrosine kinase

NSCLC:

Non-small cell lung carcinoma

PDAC:

Pancreatic ductal adenocarcinoma

PH:

Philadelphia chromosome

PNET:

Primitive neuroectodermal tumor

RCC:

Renal cell carcinoma

RY:

Receptor protein-tyrosine kinase

S/T:

Protein-serine/threonine protein kinase

SEGA:

Subependymal giant cell astrocytoma

shRNA:

Short hairpin RNA

T/Y:

Threonine/tyrosine dual specificity protein kinase

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Authors and Affiliations

  1. Department of Medical Oncology and Pneumology, University Hospital Tuebingen, Eberhard Karls University Tuebingen, Tuebingen, Germany

    Athina Moschopoulou, Stefan Zwirner, Lars Zender & Daniel Dauch

  2. German Cancer Research Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

    Athina Moschopoulou, Stefan Zwirner, Lars Zender & Daniel Dauch

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  1. Athina Moschopoulou
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Correspondence to Lars Zender or Daniel Dauch .

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  1. Eberhard Karls Universität, Pharmazeutisches Institut Eberhard Karls Universität, Tuebingen Center for Academic Drug Discovery (TueCAD2), Tübingen, Germany

    Stefan Laufer

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Funding: L.Z. and D.D. are supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [FOR2314 (D.D., L.Z.), SFB-TR209 (D.D., L.Z.,), SFB-TR240 (L.Z.), Gottfried Wilhelm Leibniz Program (L.Z.)], the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s excellence strategy – EXC 2180 – 390900677 [Image Guided and Functionally Instructed Tumour Therapies (iFIT)], the Landesstiftung Baden-Wuerttemberg [‘Improve CRC’ (D.D., L.Z.)], the European Research Council [‘CholangioConcept’ (L.Z.)] and the German Center for Translational Cancer Research (DKTK).

Ethical Approval: This chapter does not contain any studies with human participants or animals performed by of the authors.

Informed Consent: All authors have given their consent to this book chapter.

Conflict of Interest: The authors declare no competing financial interests.

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Moschopoulou, A., Zwirner, S., Zender, L., Dauch, D. (2020). Exploiting Kinase Inhibitors for Cancer Treatment: An Overview of Clinical Results and Outlook. In: Laufer, S. (eds) Proteinkinase Inhibitors. Topics in Medicinal Chemistry, vol 36. Springer, Cham. https://doi.org/10.1007/7355_2020_100

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