Related Experiment Video

Updated: Jun 23, 2026

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

KIF18A inhibitor prevents chromosomally unstable osteosarcoma growth by activating spindle assembly checkpoint

Qiang Yan1, Yan Zhang1, Pengfei Wang1

  • 1Department of Orthopedics, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Cancer Biology & Therapy
|June 22, 2026
PubMed
Abstract

Insights

Targeting KIF18A shows promise for osteosarcoma treatment. The inhibitor AM-1882 effectively reduced tumor growth in mice with minimal toxicity, offering a new therapeutic avenue.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Development

Background:

  • Osteosarcoma survival rates have stagnated due to complex genetic mutations and tumor heterogeneity.
  • Chromosomal instability in osteosarcoma presents a potential vulnerability for therapeutic intervention.
  • Kinesin family member 18A (KIF18A), an essential mitotic motor protein, was investigated as a therapeutic target.

Purpose of the Study:

  • To evaluate the efficacy of targeting KIF18A in osteosarcoma.
  • To assess the anti-cancer activity of the KIF18A inhibitor AM-1882.
  • To determine the safety profile of AM-1882 in preclinical models.

Main Methods:

  • KIF18A knockout and pharmacological inhibition were tested in osteosarcoma cell lines (SJSA1, SPT, U2OS, MG63).
  • Cell viability, survival, and proliferation were assessed following KIF18A depletion.
  • The KIF18A inhibitor AM-1882 was evaluated in cellular assays and a mouse xenograft model.

Main Results:

  • KIF18A depletion significantly impaired cell viability and proliferation in specific osteosarcoma clones (SPT).
  • Loss of KIF18A induced aberrant spindle assembly and mitotic delay, activating the spindle assembly checkpoint (SAC).
  • AM-1882 demonstrated potent anti-cancer activity, disrupted spindle assembly, reduced tumor growth in vivo, and exhibited a favorable safety profile compared to chemotherapy.

Conclusions:

  • KIF18A is a promising therapeutic target for osteosarcoma.
  • The novel KIF18A inhibitor AM-1882 exhibits significant anti-tumor efficacy.
  • AM-1882 presents a favorable safety profile, suggesting its potential as a low-toxicity therapeutic agent for osteosarcoma.
Keywords:
KIF18A inhibitorOsteosarcomaapoptosischromosome instabilityspindle assembly checkpoint

More Related Videos

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models04:25

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models

Published on: October 28, 2021

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis08:33

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 2017

Related Concept Videos

The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...