Cellular senescence in cancer treatment: friend or foe?

Kahlem, Pascal; Dörken, Bernd; Schmitt, Clemens A.

doi:10.1172/jci20784

Cited by 92 publications

(47 citation statements)

References 52 publications

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“…which is mainly regulated by p16/RB and p53/p21 pathways [16]. According to the data obtained from the findings of this study, MPTP treatment induced upregulated expression of p21 and p53, which is associated with decreased proliferation.…”

Section: Discussionsupporting

confidence: 55%

Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy

Zhu

Dong

Sun

et al. 2015

Biochemical and Biophysical Research Communications

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Section: Discussionsupporting

confidence: 55%

Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy

Zhu

Dong

Sun

et al. 2015

Biochemical and Biophysical Research Communications

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“…However, in most solid tumors, a clear relationship between apoptosis and cellular response to chemotherapy was not established. In contrast, cellular ability to undergo senescence was found recently to be associated with treatment outcome of these tumors [29][30][31][32]. We found that tetrac regulates both processes as well as the mechanisms that regulate drug transport; therefore this antagonist may have a broad use for the treatment of aggressive cancers of both hematopoietic and solid origins.…”

Section: Discussionmentioning

confidence: 80%

“…2). Since accumulating evidence indicates that cellular ability to undergo senescence or apoptotic death play key roles in chemotherapy outcome [29][30][31][32], we have tested the effect of tetrac on the corresponding pathways. As shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

Novel function of the thyroid hormone analog tetraiodothyroacetic acid: a cancer chemosensitizing and anti-cancer agent

et al. 2008

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Previous studies from our laboratory have demonstrated that thyroid hormones play a key role in cancer progression. In addition, a deaminated form, tetraiodothyroacetic acid (tetrac), that antagonizes the proliferative action of these hormones was found to possess anti-cancer functions through its ability to inhibit cellular proliferation and angiogenesis. The present study was undertaken to investigate whether tetrac could also suppress the development of drug resistance, known as a causative factor of disease relapse. Tetrac was shown to enhance cellular response in vitro to doxorubicin, etoposide, cisplatin, and trichostatin A in resistant tumor cell lines derived from neuroblastoma, osteosarcoma, and breast cancer. The mechanism of action of tetrac did not involve expression of classical drug resistance genes. However, radiolabeled doxorubicin uptake in cells was enhanced by tetrac, suggesting that one or more export mechanisms for chemotherapeutic agents are inhibited. Tetrac was also found to enhance cellular susceptibility to senescence and apoptosis, suggesting that the agent may target multiple drug resistance mechanisms. Tetrac has previously been shown to inhibit tumor cell proliferation in vitro. In vivo studies reported here revealed that tetrac in a pulsed-dose regimen was effective in suppressing the growth of a doxorubicin-resistant human breast tumor in the nude mouse. In this paradigm, doxorubicin-sensitivity was not restored, indicating that (1) the in vitro restoration of drug sensitivity by tetrac may not correlate with in vivo resistance phenomena and (2) tetrac is an effective chemotherapeutic agent in doxorubicin-resistant cells.

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“…It forms a third possible outcome of the effects of damage in addition to cell death and full repair/recovery [8,11,24,35,58,69,70,76,80]. Even cancer cells, despite multiple abnormalities, can still be forced into senescence under the action of chemotherapeutic drugs [61,63].…”

Section: Overviewmentioning

confidence: 99%

“…Although SA β-gal + cells accumulate in aging, senescent cells (detected by SA β-gal and other markers) are also present in a variety of pathological conditions, such as chronic ulcers, benign prostatic hypertrophy, atherosclerotic plaques, osteoarthritis, and tissues damaged by radiation or chemotherapy [11,33,35,69]. Their presence in neoplasms in vivo, in conjunction with other markers, has been used as evidence for the occurrence of senescence as a reaction to DNA damage and activated oncogenes in early cancer development [5,22].…”

Section: Frequency Of Senescent Cells In Tissues As a Function Of Agementioning

confidence: 99%

Senescence and life span

Hornsby¹

2009

Pflugers Arch - Eur J Physiol

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Senescence is a general cellular process that occurs as a response to stress and damage. It forms an alternative response of cells to damage that might otherwise cause programmed cell death. Whereas telomere shortening leading to telomere dysfunction was the first described cause of senescence, it is now known that senescence can result from many sources of damage. Senescent cells are found in tissues in vivo, but the cause of senescence in these cells is mostly unknown. In many cases, senescence may be the result of the action of activated oncogenes in cells. By preventing activated oncogenes from initiating a clone of neoplastic cells, senescence acts as a protective mechanism against cancer development. Until recently, the fate of senescent cells in vivo was unknown, but new evidence indicates that they are cleared by components of the innate immune system. In this way, senescence and apoptosis act as parallel pathways by which severely damaged cells are eliminated from the body. Some senescent cells persist in tissues, in some cases increasing in frequency as a function of age. It is hypothesized that these persistent senescent cells have adverse effects on tissue function. If so, senescence may be an example of antagonistic pleiotropy, providing an anticancer mechanism in early life but having adverse effects on tissue function in late life. Much more research is needed to address the broader question of the overall impact of senescence on life span.

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Cellular senescence in cancer treatment: friend or foe?

Cited by 92 publications

References 52 publications

Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy

Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy

Novel function of the thyroid hormone analog tetraiodothyroacetic acid: a cancer chemosensitizing and anti-cancer agent

Senescence and life span

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