Review
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Therapy-induced cellular senescence: Potentiating tumor elimination or driving cancer resistance and recurrence?
Version 1
: Received: 2 June 2024 / Approved: 3 June 2024 / Online: 3 June 2024 (09:54:54 CEST)
A peer-reviewed article of this Preprint also exists.
Liu, Y.; Lomeli, I.; Kron, S.J. Therapy-Induced Cellular Senescence: Potentiating Tumor Elimination or Driving Cancer Resistance and Recurrence? Cells 2024, 13, 1281. Liu, Y.; Lomeli, I.; Kron, S.J. Therapy-Induced Cellular Senescence: Potentiating Tumor Elimination or Driving Cancer Resistance and Recurrence? Cells 2024, 13, 1281.
Abstract
Cellular senescence has recently been recognized as a hallmark of cancer, reflecting its association with aging and inflammation, its role as a response to deregulated proliferation and oncogenic stress, and its induction by cancer therapies such as radiation, chemotherapy, and targeted agents. While such therapy-induced senescence (TIS) has been linked to resistance, recurrence, metastasis and normal tissue toxicity, TIS has the potential to enhance therapy response and stimulate anti-tumor immunity. In this review, we examine the Jekyll and Hyde nature of senescent cells (SnCs), with a particular focus on how their persistence while expressing the senescence-associated secretory phenotype (SASP) modulates the tumor microenvironment through autocrine and paracrine mechanisms. Via the SASP, the formation of SnCs may alternately mediate resistance or response to conventional therapy. Further, toward fulfilling the unmet potential of cancer immunotherapy, we consider how SnCs may influence tumor inflammation and serve as a source of antigen to potentiate anti-tumor immunity. This new view suggests treatment strategies based on inducing TIS to enhance immune checkpoint blockade. Finally, we describe strategies for mitigating the detrimental effects of senescence, such as modulating the SASP or targeting SnC persistence, toward enhancing the benefits of cancer treatment.
Keywords
senescence; SASP (senescence‐associated secretory phenotype); immune surveillance; immunosuppression; senolytics; tumor microenvironment; cancer therapy; therapy resistance
Subject
Biology and Life Sciences, Other
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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