Hellmich Charlotte, Moore Jamie A, Bowles Kristian M, Rushworth Stuart A
Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
Department of Haematology, Norfolk and Norwich University Hospitals NHS Trust, Norwich, United Kingdom.
Front Oncol. 2020 Feb 25;10:230. doi: 10.3389/fonc.2020.00230. eCollection 2020.
Senescence is the irreversible arrest of cell proliferation that has now been shown to play an important role in both health and disease. With increasing age senescent cells accumulate throughout the body, including the bone marrow and this has been associated with a number of age-related pathologies including malignancies. It has been shown that the senescence associated secretory phenotype (SASP) creates a pro-tumoural environment that supports proliferation and survival of malignant cells. Understanding the role of senescent cells in tumor development better may help us to identify new treatment targets to impair tumor survival and reduce treatment resistance. In this review, we will specifically discuss the role of senescence in the aging bone marrow (BM) microenvironment. Many BM disorders are age-related diseases and highly dependent on the BM microenvironment. Despite advances in drug development the prognosis particularly for older patients remains poor and new treatment approaches are needed to improve outcomes for patients. In this review, we will focus on the relationship of senescence and hematological malignancies, how senescence promotes cancer development and how malignant cells induce senescence.
细胞衰老指细胞增殖的不可逆停滞,现已证明其在健康和疾病中均发挥重要作用。随着年龄增长,衰老细胞在全身各处积聚,包括骨髓,这与多种与年龄相关的病理状况(包括恶性肿瘤)有关。研究表明,衰老相关分泌表型(SASP)营造了一种促肿瘤环境,支持恶性细胞的增殖和存活。更好地了解衰老细胞在肿瘤发生中的作用,可能有助于我们确定新的治疗靶点,以损害肿瘤存活并降低治疗抗性。在本综述中,我们将具体讨论衰老在衰老骨髓(BM)微环境中的作用。许多BM疾病都是与年龄相关的疾病,且高度依赖于BM微环境。尽管药物研发取得了进展,但尤其是老年患者的预后仍然很差,需要新的治疗方法来改善患者的治疗效果。在本综述中,我们将重点关注衰老与血液系统恶性肿瘤的关系、衰老如何促进癌症发展以及恶性细胞如何诱导衰老。