Escape from senescence: molecular basis and therapeutic ramifications

TY - JOUR

T1 - Escape from senescence

T2 - molecular basis and therapeutic ramifications

AU - Evangelou, Konstantinos

AU - Belogiannis, Konstantinos

AU - Papaspyropoulos, Angelos

AU - Petty, Russell

AU - Gorgoulis, Vassilis G.

N1 - Funding Information: Ministry of Development and Investment/General Secretariat for Research and Innovation-Flagship Initiative to address SARS-CoV-2. Grant Number: 2020ΣΕ01300001; Flagship Initiative to address SARS-CoV-2. Grant Number: 2020ΣΕ01300001; European Regional Development Fund European Union and Greek National Funds; RESEARCH-CREATE-INNOVATE. Grant Numbers: T2EDK-03266, T2EDK-02939; Sonia Kotopoulos Hellenic Foundation for Research and Innovation. Grant Number: 3782; National and Kapodistrian University of Athens-Special Account for Research Grants (SARG). Grant Number: 70/3/8916; Foundation for Education and European Culture (IPEP). Copyright: © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

PY - 2023/8

Y1 - 2023/8

N2 - Cellular senescence constitutes a stress response mechanism in reaction to a plethora of stimuli. Senescent cells exhibit cell-cycle arrest and altered function. While cell-cycle withdrawal has been perceived as permanent, recent evidence in cancer research introduced the so-called escape-from-senescence concept. In particular, under certain conditions, senescent cells may resume proliferation, acquiring highly aggressive features. As such, they have been associated with tumour relapse, rendering senescence less effective in inhibiting cancer progression. Thus, conventional cancer treatments, incapable of eliminating senescence, may benefit if revisited to include senolytic agents. To this end, it is anticipated that the assessment of the senescence burden in everyday clinical material by pathologists will play a crucial role in the near future, laying the foundation for more personalised approaches. Here, we provide an overview of the investigations that introduced the escape-from-senescence phenomenon, the identified mechanisms, as well as the major implications for pathology and therapy.

AB - Cellular senescence constitutes a stress response mechanism in reaction to a plethora of stimuli. Senescent cells exhibit cell-cycle arrest and altered function. While cell-cycle withdrawal has been perceived as permanent, recent evidence in cancer research introduced the so-called escape-from-senescence concept. In particular, under certain conditions, senescent cells may resume proliferation, acquiring highly aggressive features. As such, they have been associated with tumour relapse, rendering senescence less effective in inhibiting cancer progression. Thus, conventional cancer treatments, incapable of eliminating senescence, may benefit if revisited to include senolytic agents. To this end, it is anticipated that the assessment of the senescence burden in everyday clinical material by pathologists will play a crucial role in the near future, laying the foundation for more personalised approaches. Here, we provide an overview of the investigations that introduced the escape-from-senescence phenomenon, the identified mechanisms, as well as the major implications for pathology and therapy.

KW - cellular senescence

KW - senescence escape

KW - cancer

KW - pathology

KW - senolytics

KW - therapy

UR - https://www.scopus.com/pages/publications/85166947516

U2 - 10.1002/path.6164

DO - 10.1002/path.6164

M3 - Review article

C2 - 37550877

SN - 0022-3417

VL - 260

SP - 649

EP - 665

JO - The Journal of Pathology

JF - The Journal of Pathology

IS - 5

ER -