Evidence map›Paper›PMID 29142107›Full record

ReviewOpen biology2017

Is inflammatory micronucleation the key to a successful anti-mitotic cancer drug?

T J Mitchison, J Pineda, J Shi, S Florian

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Open biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
3.1field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 76 citations in OpenAlex.

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  19. Molecular Link between DNA Damage Response and Microtubule Dynamics.International journal of molecular sciences · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 2 countries.

T J MitchisonDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA timothy_mitchison@hms.harvard.edu.ORCID 0000-0001-7781-1897
J PinedaDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA.
J ShiHong Kong Baptist University, Kowloon, HK, Hong Kong.
S FlorianDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA.
Harvard University · USHong Kong Baptist University · HK

Funding

MICROTUBULE DYNAMICS AND MITOTIC MECHANISMR01GM039565 · NIGMS · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI MITCHISON, TIMOTHY J · 1988 to 2018
$6.2M
NIGMS NIH HHS R01 GM039565
6 · The paper itself

Abstract

Paclitaxel is a successful anti-cancer drug that kills cancer cells in two-dimensional culture through perturbation of mitosis, but whether it causes tumour regression by anti-mitotic actions is controversial. Drug candidates that specifically target mitosis, including inhibitors of kinesin-5, AurkA, AurkB and Plk1, disappointed in the clinic. Current explanations for this discrepancy include pharmacokinetic differences and hypothetical interphase actions of paclitaxel. Here, we discuss post-mitotic micronucleation as a special activity of taxanes that might explain their higher activity in solid tumours. We review data showing that cells which exit mitosis in paclitaxel are highly micronucleated and suffer post-mitotic DNA damage, and that these effects are much stronger for paclitaxel than kinesin-5 inhibitors. We propose that post-mitotic micronucleation promotes inflammatory signalling via cGAS-STING and other pathways. In tumours, this signalling may recruit cytotoxic leucocytes, damage blood vessels and prime T-cell responses, leading to whole-tumour regression. We discuss experiments that are needed to test the micronucleation hypothesis, and its implications for novel anti-mitotic targets and enhancement of taxane-based therapies.

Indexed as

AnimalsAnti-Inflammatory AgentsAntimitotic AgentsAntineoplastic AgentsHumansMicronuclei, Chromosome-DefectiveNeoplasmsPaclitaxelAnti-Inflammatory AgentsAntimitotic AgentsAntineoplastic AgentsPaclitaxelanti-mitoticcancerchemotherapyinflammationkinesin-5paclitaxel

Identifiers

PMID29142107
PMCPMC5717346
OpenAlexW2769634826

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.