Cancer Cells Display Profound Intra- and Interline Variation following Prolonged Exposure to Antimitotic Drugs

Gascoigne, Karen E.; Taylor, Stephen S.

doi:10.1016/j.ccr.2008.07.002

Cited by 745 publications

(1,005 citation statements)

References 46 publications

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“…Cell cycle checkpoint inhibitors in combination with DNA-damaging agents enhance MC by inducing 'mitotic slippage'. A recent study has used automated time-lapsed video microscopy to provide insights into the fate of individual cells entering catastrophic mitotic arrest after antimitotic drug treatment (Gascoigne and Taylor, 2008). A panel of cell lines treated with several antimitotic drugs displayed significant inter-as well as intra-cell line differences in cellular responses, including death by apoptosis during mitosis (that is, 'mitotic death'), or death post-mitosis in cells that slipped into interphase (that is, exit mitotic arrest) (Gascoigne and Taylor, 2008).…”

Section: Clinical Relevance Of Cell Death Pathwaysmentioning

confidence: 99%

“…A recent study has used automated time-lapsed video microscopy to provide insights into the fate of individual cells entering catastrophic mitotic arrest after antimitotic drug treatment (Gascoigne and Taylor, 2008). A panel of cell lines treated with several antimitotic drugs displayed significant inter-as well as intra-cell line differences in cellular responses, including death by apoptosis during mitosis (that is, 'mitotic death'), or death post-mitosis in cells that slipped into interphase (that is, exit mitotic arrest) (Gascoigne and Taylor, 2008). Importantly, the variation in daughtercell responses to the division of a single parent cell after antimitotic drug challenge illustrates that intra-cell line variation is not owing to a genetic predisposition.…”

Section: Clinical Relevance Of Cell Death Pathwaysmentioning

confidence: 99%

“…Cells, which breach a threshold of cell death signaling, die during mitotic arrest, whereas cells, which breach a mitosis exit threshold by cyclin B1 degradation, enter interphase. These post-mitotic cells may subsequently vary in their responses, which include cell death, prolonged arrest or abnormal cell divisions, possibly guided by similar signaling thresholds (Gascoigne and Taylor, 2008).…”

Section: Clinical Relevance Of Cell Death Pathwaysmentioning

confidence: 99%

“…Moreover, each type of cellular response results in a very different clonogenic potential. Although such information may appear conflicting, viewing cellular responses as an orchestrated interplay of various competing pathways (Gascoigne and Taylor, 2008) may alter our perspectives on tumor responses to anticancer treatments.…”

Section: Clinical Relevance Of Cell Death Pathwaysmentioning

confidence: 99%

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Harnessing the complexity of DNA-damage response pathways to improve cancer treatment outcomes

et al. 2010

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Section: Clinical Relevance Of Cell Death Pathwaysmentioning

confidence: 99%

Section: Clinical Relevance Of Cell Death Pathwaysmentioning

confidence: 99%

Section: Clinical Relevance Of Cell Death Pathwaysmentioning

confidence: 99%

Section: Clinical Relevance Of Cell Death Pathwaysmentioning

confidence: 99%

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Harnessing the complexity of DNA-damage response pathways to improve cancer treatment outcomes

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“…STLC, like monastrol and most if not all of the known Eg5 inhibitors, also inhibits mitosis, promoting the characteristic mono-astral spindle phenotype [10,17]. Induction of aberrant mitosis in tumor cells leads to consequent mitotic arrest, which is often followed by apoptotic cell death [18,19]. The fact that Eg5 inhibition in cancer cells results in a prolonged arrest in mitosis and an increased incidence of apoptosis has validated the apoptotic properties of Eg5 inhibitors [19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Mutations in the human kinesin Eg5 that confer resistance to monastrol and S-trityl-l-cysteine in tumor derived cell lines

Tcherniuk

Lis

Kozielski

et al. 2010

Biochemical Pharmacology

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. Mutations in the human kinesin Eg5 that confer resistance to monastrol and S-Trityl-L-Cysteine in tumor derived cell lines.. Biochemical Pharmacology, Elsevier, 2010, 79 (6) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. confirms the target specificity of monastrol and STLC for Eg5. These data also suggest a possible mechanism by which drug resistance may occur in tumors treated with agents targeting Eg5.

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Microtubule Inhibitors

Galletti¹,

Giannakakou²

2023

Holland‐Frei Cancer Medicine

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Overview Central to the ever‐growing list of anticancer therapies is the microtubule inhibitors (MTIs), a class of naturally derived compounds that bind tubulin or microtubules and disrupt the function of the cell's cytoskeleton. The vinca alkaloids were among the first drugs to receive FDA approval for the treatment of cancer, even before the α/β‐tubulin dimer was identified as their target. Today, 60 years from their entry to the clinic, these microtubule‐destabilizing drugs continue to be central in current and widely used chemotherapy regimens. Paclitaxel was the first natural product identified to bind microtubule polymers instead of soluble tubulin dimers, and the prototype of the new class of microtubule‐stabilizing drugs. Together, both destabilizing and stabilizing drugs form the family of MTIs, which continues to expand with the clinical approval of several other plant‐, marine sponge‐ and bacteria‐derived compounds, such as epothilones, halicondrin B, maytansinoids, and auristatins. Even in the current era of targeted therapies and immune checkpoint inhibitors, MTIs are among the most effective drugs for the treatment of solid tumors and hematologic malignancies. For decades, these drugs were thought to exert their antitumor activity solely by inhibiting cancer cell division. Current evidence demonstrates that MTIs can effectively kill not only dividing but also nondividing interphase cells, which represent the most abundant cell population in patient tumors. In this chapter, we will discuss MTI mechanism of action or “inaction,” all the way from molecular interactions to cancer cell effects to patient treatment. Fundamental to this chapter is the thesis that MTIs are “targeted therapies,” which is a big departure from the established view that these drugs are nonspecific, generally cytotoxic chemotherapy drugs. Once accepted, this thesis provides previously unrecognized opportunities for precision oncology, taking advantage of the distinct functions and alterations of the MT cytoskeleton in different tumor types and individual patients.

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Cancer Cells Display Profound Intra- and Interline Variation following Prolonged Exposure to Antimitotic Drugs

Cited by 745 publications

References 46 publications

Harnessing the complexity of DNA-damage response pathways to improve cancer treatment outcomes

Harnessing the complexity of DNA-damage response pathways to improve cancer treatment outcomes

Mutations in the human kinesin Eg5 that confer resistance to monastrol and S-trityl-l-cysteine in tumor derived cell lines

Microtubule Inhibitors

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