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Related Concept Videos

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Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...

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Related Experiment Video

Updated: Jul 26, 2026

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures
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Multi-Omic Evaluation of PLK1 Inhibitor-Onvansertib-In Colorectal Cancer Spheroids.

Brian D Fries1, Emily R Sekera1, Joseph H Holbrook2

  • 1Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, USA.

Journal of Mass Spectrometry : JMS
|April 8, 2025
PubMed
Summary

Onvansertib, a Polo-like kinase 1 (Plk1) inhibitor, halts cell cycle progression in colorectal cancer (CRC) spheroids. This study reveals Plk1 inhibition alters cell cycle proteins and phosphatidylcholine lipids, suggesting S-phase arrest.

Keywords:
Plk‐1 inhibitioncell cyclecolorectal cancerlipidomicsmass spectrometry imagingproteomicsspatial lipidomicsspheroids

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Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Pharmacology

Background:

  • Polo-like kinase 1 (Plk1) is a key cell cycle regulator implicated in chemotherapy resistance and poor patient survival.
  • Plk1 inhibitors, like onvansertib, are investigated for cancer treatment, including KRAS mutant colorectal cancers (CRCs).

Purpose of the Study:

  • To investigate the molecular effects of onvansertib on HCT 116 colorectal cancer spheroids using proteomics and lipidomics.
  • To determine the time-course of onvansertib accumulation and its impact on cellular processes.

Main Methods:

  • Untargeted liquid chromatography-mass spectrometry (LC-MS) for proteomics and lipidomics.
  • Mass spectrometry imaging (MSI) to track onvansertib distribution.
  • 72-hour time-course experiment on HCT 116 spheroids.

Main Results:

  • Onvansertib accumulated in spheroids starting at 12 hours and persisting through 72 hours.
  • Proteomics revealed alterations in cell cycle proteins, increased aurora kinase B and Borealin, and changes in lipid metabolism enzymes.
  • Lipidomics showed significant alterations in phosphatidylcholine lipids, with dynamic changes in abundance over the treatment period.

Conclusions:

  • Onvansertib treatment leads to cell cycle arrest, likely in the S phase, in colorectal cancer spheroids.
  • Observed changes in cell cycle proteins and phosphatidylcholine lipid profiles provide insights into onvansertib's mechanism of action.
  • These findings support the therapeutic potential of onvansertib in KRAS mutant colorectal cancers.