Related Experiment Video

Updated: Jun 5, 2025

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

6.7K

Low PPP2R2A expression promotes sensitivity to CHK1 inhibition in high-grade serous ovarian cancer

Zhaojun Qiu1, Deepika Sigh1, Yujie Liu1

  • 1Department of Radiation Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio-43210, United States.

Theranostics
|December 11, 2024
PubMed

Insights

Deficiency in PPP2R2A enhances sensitivity to CHK1 inhibitors in high-grade serous ovarian cancer (HGSOC). This finding identifies PPP2R2A as a predictive biomarker and therapeutic target for HGSOC, potentially overcoming PARP inhibitor resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • High-grade serous ovarian cancer (HGSOC) remains a lethal disease with limited treatment options, despite PARP inhibitors.
  • Checkpoint kinase 1 (CHK1) inhibitors show promise for ovarian cancer, but a predictive biomarker is needed to optimize efficacy and reduce toxicity.
  • The role of PP2A B55α (encoded by PPP2R2A) in CHK1 inhibitor sensitivity varies across cancer types.

Purpose of the Study:

  • To investigate whether PPP2R2A deficiency enhances the sensitivity of HGSOC to CHK1 inhibition.
  • To identify potential predictive biomarkers for CHK1 inhibitor therapy in HGSOC.
  • To explore therapeutic strategies to overcome PARP inhibitor resistance in HGSOC.

Main Methods:

  • HGSOC cells with PPP2R2A knockdown or naturally low PPP2R2A expression were treated with a CHK1 inhibitor.
  • Cell growth was assessed using in vitro and in vivo assays.
  • Mechanisms of enhanced sensitivity, including replication stress (RS), were investigated using molecular biology techniques like western blotting, immunofluorescence, and DNA fiber assays.

Main Results:

  • PPP2R2A knockdown elevated c-Myc-induced replication stress (RS) by upregulating replication initiation.
  • HGSOC cells with PPP2R2A deficiency became reliant on CHK1 for survival.
  • This enhanced sensitivity was observed even in HGSOC cells resistant to PARP inhibitors.

Conclusions:

  • PPP2R2A/PP2A B55α is identified as a potential predictive biomarker for CHK1 inhibitor sensitivity in HGSOC.
  • PPP2R2A/PP2A B55α represents a potential therapeutic target to improve HGSOC treatment outcomes.
  • Targeting PPP2R2A may offer a strategy to overcome resistance to PARP inhibitors in HGSOC.

More Related Videos

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer09:40

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

2.6K
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

7.2K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.7K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.1K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.4K