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Proceedings of the National Academy of Sciences of the United States of America, volume 116, issue 24, pages 201816012

My journey from tyrosine phosphorylation inhibitors to targeted immune therapy as strategies to combat cancer

Levitzki Alexander ¹

Klein Shoshana ¹

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Unit of Cellular Signaling, Department of Biological Chemistry, Silberman Life Sciences Institute, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel |

Publication type: Journal Article

Publication date: 2019-05-10

Proceedings of the National Academy of Sciences (PNAS)

Journal: Proceedings of the National Academy of Sciences of the United States of America

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Impact factor: 11.1

ISSN: 00278424, 10916490

DOI: 10.1073/pnas.1816012116

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PubMed ID: 31076554

Multidisciplinary

Abstract

Significance This paper discusses the successes and failures of tyrosine kinase inhibitors in treating cancer, and why we believe targeted immunotherapy may provide more durable remissions. Tyrosine kinases are central to tumor development and progression. Since we originally demonstrated specific inhibition of tyrosine kinases, with minimal toxicity, a large number of tyrosine kinase inhibitors—both small molecules and antibodies—have entered the clinic. Nonetheless, tumors are heterogeneous and highly mutable, and they eventually bypass tyrosine kinase inhibition. The immune system has the ability to seek and destroy tumor cells. Tumors avoid detection by the immune system, so the goal is to reinstate immune surveillance against the tumor. Since the 1980s there has been a drive toward personalized targeted therapy for cancer. “Targeted cancer therapy” originally focused on inhibiting essential tumor survival factors, primarily protein tyrosine kinases. The complexity and rapid mutability of tumors, however, enable them to develop resistance to tyrosine kinase inhibitors (TKIs), even when these are multitargeted or applied in combination. This has led to the development of targeted cancer immunotherapy, to enhance immune surveillance against the tumor. In this paper, we provide a personal view of the development of targeted therapy, from TKIs to targeted immunotherapy.

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Citations by journals

	1
Frontiers in Pharmacology	Frontiers in Pharmacology, 1, 7.69% Frontiers in Pharmacology 1 publication, 7.69%
Current Medicinal Chemistry	Current Medicinal Chemistry, 1, 7.69% Current Medicinal Chemistry 1 publication, 7.69%
Medicine (United States)	Medicine (United States), 1, 7.69% Medicine (United States) 1 publication, 7.69%
Molecules	Molecules, 1, 7.69% Molecules 1 publication, 7.69%
Frontiers in Oncology	Frontiers in Oncology, 1, 7.69% Frontiers in Oncology 1 publication, 7.69%
Applied Materials Today	Applied Materials Today, 1, 7.69% Applied Materials Today 1 publication, 7.69%
Biochimica et Biophysica Acta - Molecular Basis of Disease	Biochimica et Biophysica Acta - Molecular Basis of Disease, 1, 7.69% Biochimica et Biophysica Acta - Molecular Basis of Disease 1 publication, 7.69%
Computers in Biology and Medicine	Computers in Biology and Medicine, 1, 7.69% Computers in Biology and Medicine 1 publication, 7.69%
Arabian Journal of Chemistry	Arabian Journal of Chemistry, 1, 7.69% Arabian Journal of Chemistry 1 publication, 7.69%
Cancers	Cancers, 1, 7.69% Cancers 1 publication, 7.69%
Methods in Molecular Biology	Methods in Molecular Biology, 1, 7.69% Methods in Molecular Biology 1 publication, 7.69%
Proceedings of the National Academy of Sciences of the United States of America	Proceedings of the National Academy of Sciences of the United States of America, 1, 7.69% Proceedings of the National Academy of Sciences of the United States of America 1 publication, 7.69%
	1

Citations by publishers

	1 2 3
Elsevier	Elsevier, 3, 23.08% Elsevier 3 publications, 23.08%
Frontiers Media S.A.	Frontiers Media S.A., 2, 15.38% Frontiers Media S.A. 2 publications, 15.38%
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 2, 15.38% Multidisciplinary Digital Publishing Institute (MDPI) 2 publications, 15.38%
Bentham Science	Bentham Science, 1, 7.69% Bentham Science 1 publication, 7.69%
Wolters Kluwer Health	Wolters Kluwer Health, 1, 7.69% Wolters Kluwer Health 1 publication, 7.69%
King Saud University	King Saud University, 1, 7.69% King Saud University 1 publication, 7.69%
Springer Nature	Springer Nature, 1, 7.69% Springer Nature 1 publication, 7.69%
Proceedings of the National Academy of Sciences (PNAS)	Proceedings of the National Academy of Sciences (PNAS), 1, 7.69% Proceedings of the National Academy of Sciences (PNAS) 1 publication, 7.69%
	1 2 3

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Levitzki A., Klein S. My journey from tyrosine phosphorylation inhibitors to targeted immune therapy as strategies to combat cancer // Proceedings of the National Academy of Sciences of the United States of America. 2019. Vol. 116. No. 24. p. 201816012.

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RIS |

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RIS Copy

TY - JOUR

DO - 10.1073/pnas.1816012116

UR - https://doi.org/10.1073%2Fpnas.1816012116

TI - My journey from tyrosine phosphorylation inhibitors to targeted immune therapy as strategies to combat cancer

T2 - Proceedings of the National Academy of Sciences of the United States of America

AU - Levitzki, Alexander

AU - Klein, Shoshana

PY - 2019

DA - 2019/05/10 00:00:00

PB - Proceedings of the National Academy of Sciences (PNAS)

SP - 201816012

IS - 24

VL - 116

PMID - 31076554

SN - 0027-8424

SN - 1091-6490

ER -

BibTex |

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@article{2019_Levitzki,

author = {Alexander Levitzki and Shoshana Klein},

title = {My journey from tyrosine phosphorylation inhibitors to targeted immune therapy as strategies to combat cancer},

journal = {Proceedings of the National Academy of Sciences of the United States of America},

year = {2019},

volume = {116},

publisher = {Proceedings of the National Academy of Sciences (PNAS)},

month = {may},

url = {https://doi.org/10.1073%2Fpnas.1816012116},

number = {24},

pages = {201816012},

doi = {10.1073/pnas.1816012116}

}

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Levitzki, Alexander, and Shoshana Klein. “My journey from tyrosine phosphorylation inhibitors to targeted immune therapy as strategies to combat cancer.” Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 24, May. 2019, p. 201816012. https://doi.org/10.1073%2Fpnas.1816012116.

Found error?

Publisher

Proceedings of the National Academy of Sciences (PNAS)

Journal

Proceedings of the National Academy of Sciences of the United States of America

Quartile SCImago

Quartile WOS

Impact factor

11.1

ISSN

00278424 (Print)
10916490 (Electronic)