Senescence and senotherapeutics: a new field in cancer therapy

Vassilios Myrianthopoulos; Konstantinos Evangelou; Panagiotis V S Vasileiou; Tomer Cooks; Theodoros P Vassilakopoulos; Gerassimos A Pangalis; Myrsini Kouloukoussa; Christos Kittas; Alexandros G Georgakilas; Vassilis G Gorgoulis

doi:10.1016/j.pharmthera.2018.08.006

Senescence and senotherapeutics: a new field in cancer therapy

Pharmacol Ther. 2019 Jan:193:31-49. doi: 10.1016/j.pharmthera.2018.08.006. Epub 2018 Aug 16.

Affiliations

¹ Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Division of Pharmaceutical Chemistry, School of Pharmacy, National and Kapodistrian University of Athens, Greece; PharmaInformatics Unit, Athena Research Center, Greece.
² Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Department of Anatomy-Histology-Embryology, Medical School, University of Ioannina, Ioannina, Greece.
³ Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
⁴ The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.
⁵ Department of Haematology and Bone Marrow Transplantation, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
⁶ Department of Haematology, Athens Medical Center, Psychikon, Athens, Greece.
⁷ Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Museum of Anthropology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
⁸ DNA Damage Laboratory, Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Athens, Greece. Electronic address: alexg@mail.ntua.gr.
⁹ Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Center for New Biotechnologies and Precision Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Faculty Institute for Cancer Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK; Biomedical Research Foundation, Academy of Athens, Athens, Greece. Electronic address: vgorg@med.uoa.gr.

PMID: 30121319
DOI: 10.1016/j.pharmthera.2018.08.006

Abstract

Cellular senescence is a stress response mechanism ensuring homeostasis. Its temporal activation during embryonic development or normal adult life is linked with beneficial properties. In contrast, persistent (chronic) senescence seems to exert detrimental effects fostering aging and age-related disorders, such as cancer. Due to the lack of a reliable marker able to detect senescence in vivo, its precise impact in age-related diseases is to a large extent still undetermined. A novel reagent termed GL13 (SenTraGor^TM) that we developed, allowing senescence recognition in any type of biological material, emerges as a powerful tool to study the phenomenon of senescence in vivo. Exploiting the advantages of this novel methodological approach, scientists will be able to detect and connect senescence with aggressive behavior in human malignancies, such as tolerance to chemotherapy in classical Hodgkin Lymphoma and Langerhans Cell Histiocytosis. The latter depicts the importance of developing the new and rapidly expanding field of senotherapeutic agents targeting and driving to cell death senescent cells. We discuss in detail the current progress of this exciting area of senotherapeutics and suggest its future perspectives and applications.

Keywords: Cancer; Hodgkin; Langerhans Cell Histiocytosis; Lymphoma; SenTraGor(TM); Senescence; Senotherapeutics-Senolytics.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antineoplastic Agents / therapeutic use*
Cellular Senescence*
Humans
Neoplasms / drug therapy*

Substances

Antineoplastic Agents