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Paul J Cancer Metastasis Treat 2020;6:29 Journal of Cancer
DOI: 10.20517/2394-4722.2020.63 Metastasis and Treatment

Review Open Access

The systemic hallmarks of cancer

Doru Paul

Medical Oncology, Weill Cornell Medicine, New York, NY 10021, USA.

Correspondence to: Dr. Doru Paul, Medical Oncology, Weill Cornell Medicine, 1305 York Avenue 12th Floor, New York, NY
10021, USA. E-mail: dop9054@med.cornell.edu

How to cite this article: Paul D. The systemic hallmarks of cancer. J Cancer Metastasis Treat 2020;6:29.
http://dx.doi.org/10.20517/2394-4722.2020.63

Received: 19 Jun 2020 First Decision: 17 Jul 2020 Revised: 22 Jul 2020 Accepted: 6 Aug 2020 Published: 28 Aug 2020
Academic Editor: Ciro Isidoro Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Cancer is not just a lump of cells that divide, invade, and spread randomly, but rather a multi-layered precisely
tuned process that requires the participation of the whole organism. There is an urgent need to zoom-out from
the cellular and the local stromal view and broaden our perspective by including the whole organism level.
Geographically separated cancer tissues communicate between themselves, forming a system that interacts
with the rest of the organism through cancer induced systemic pathogenic networks. In the present paper, I
introduce six systemic hallmarks of cancer that emerge as a result of these interactions. I also describe several
potential therapeutic approaches that can be developed using the cancer system concept. Overall, I argue that
the tumoricentric paradigm should be replaced with a broader approach that brings into focus the “cancerized”
organism.

Keywords: Cancer system, metastasis, cancer hallmarks, organism, tissue, system of cancer, systemic networks,
system biology

INTRODUCTION
The cancer system
From the systemic biology point of view, organisms are complex, embedded, multi-layered networks
of interactions. At the cellular level, the networks are comprised of genes, metabolic intermediates,
miRNA and signaling molecules (proteins, lipids, ions). At the tissular level, the networks are comprised
of interactions between different cell types and between the cells and the supporting stroma. At the

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
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