On the bright side, polo-like kinase 1 (PLK1) is considered a master regulator of the ever-important cell cycle. On the dark side, PLK1 expression (at both the mRNA and protein level) has shown to be upregulated in tumor cells, suggesting that PLK1 may also contribute to tumorigenesis. Despite this direct association, researchers studying the role of PLK1 in cancer have encountered a problem: a lack of appropriate animal models for experimentation.

“Even though studies have suggested that PLK1 contributes to tumorigenesis, the ability of PLK1 to drive oncogenic transformation on its own in vivo was still questionable due to a lack of sophisticated animal models for experimentation [18, 19].”

This problem may have been solved in 2021. In a new editorial paper, researchers Lilia Gheghiani and Zheng Fu from Virginia Commonwealth University discuss a recent study using their team’s new genetically engineered mouse (GEM) model to assess the ability of PLK1 to be a sole driver of oncogenic transformation in vivo. Their editorial was published in Oncotarget’s Volume 14 on June 27, 2023, and entitled, “The dark side of PLK1: Implications for cancer and genomic instability.”

Full blog - https://www.oncotarget.org/2023/06/29/novel-gem-model-unveils-plk1s-role-in-tumorigenesis/

Paper DOI - https://doi.org/10.18632/oncotarget.28456

Correspondence to -  Zheng Fu - zheng.fu@vcuhealth.org

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Keywords - cancer, polo-like kinase 1 (PLK1), oncogene, chromosomal instability, cell cycle checkpoints, tumorigenesis

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Novel GEM Model Unveils PLK1’s Role in Tumorigenesis

BUFFALO, NY - June 3, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 19, 2025, titled “PRDX1 protects ATM from arsenite-induced proteotoxicity and maintains its stability during DNA damage signaling."

In this study, led by first author Reem Ali and corresponding author Dindial Ramotar from Hamad Bin Khalifa University in Qatar, researchers discovered that a protein called PRDX1 helps maintain the stability of ATM, a key protein involved in repairing damaged DNA, especially when cells are under stress from arsenite exposure. The study found that without PRDX1, cells lose their ability to repair DNA and become more sensitive to chemotherapy. This finding suggests that targeting PRDX1 could improve the success of some cancer treatments.

PRDX1 is already known for its role in protecting cells from oxidative damage, but this study shows it also plays a role in the DNA repair process. ATM is an essential protein that detects breaks in DNA and starts the repair process. When PRDX1 is missing, ATM is rapidly lost, especially when cells are exposed to arsenite, a toxic substance found in the environment. Without ATM, the DNA repair system fails, leaving cells more vulnerable to damage.

By using both human cell lines and clinical samples from ovarian cancer patients, the team showed that high levels of PRDX1, along with ATM and MRE11 (another DNA repair protein), were linked to tumors' aggressive features and lower patient survival rates. This pattern suggests that tumors with high PRDX1 may resist chemotherapy by increasing their DNA repair capacity. On the other hand, removing PRDX1 weakened the repair system and made cancer cells more responsive to DNA-damaging platinum drugs.

The study also showed that combining low doses of arsenite with drugs that either block ATM or damage DNA caused a much higher rate of cancer cell death in cells that lacked PRDX1. These results suggest a new treatment approach: lowering PRDX1 levels to make cancer cells more sensitive to DNA-damaging platinum therapies already in use. This highlights PRDX1 not only as a protector of cell function but also as a potential weak point in cancer cells.

“As such, we propose that small molecule inhibitors of PRDX1, or single nucleotide polymorphisms that compromise PRDX1 function, in combination with low doses of arsenite can be exploited to treat chemo-resistant tumours.”

These findings open the door for the use of PRDX1 as a biomarker to predict treatment response and as a promising target for new combination therapies. For patients with ovarian cancer and potentially other tumors, adjusting PRDX1 levels may help overcome drug resistance and improve outcomes.

DOI - https://doi.org/10.18632/oncotarget.28720

Correspondence to: Dindial Ramotar - dramotar@hbku.edu.qa

Video short - https://www.youtube.com/watch?v=suOhF7mPlNQ

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Keywords - cancer, redox signaling, homologous recombination, protein interaction, cell cycle, protein modification

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Blocking PRDX1 Protein May Improve Chemotherapy Response in Ovarian Cancer

Scientists have uncovered a promising new strategy to weaken cancer cells’ natural defense mechanisms, potentially making chemotherapy more effective. In a study published in Volume 16 of Oncotarget, researchers identified the protein PRDX1 as a key player in helping tumors resist treatment. By targeting this protein, they propose a novel way to combat aggressive, treatment-resistant cancers.

Understanding Why Some Cancers Resist Treatment

Chemotherapy works by damaging the DNA of cancer cells, forcing them to self-destruct. However, many cancers develop robust repair systems that fix this damage, allowing the tumor to survive and grow. A central component of this repair machinery is a protein called ATM, which acts like a first responder in the cell, detecting DNA damage and coordinating its repair.

In ovarian cancer and other aggressive tumors, high levels of ATM have been associated with poor survival rates and resistance to chemotherapy.

The Study: How PRDX1 Protects Cancer Cells

The study, titled “PRDX1 protects ATM from arsenite-induced proteotoxicity and maintains its stability during DNA damage signaling,” was led by first author Reem Ali and corresponding author Dindial Ramotar from Hamad Bin Khalifa University in Qatar, in collaboration with researchers from the University of Nottingham in the UK. 

Full blog - https://www.oncotarget.org/2025/07/14/prdx1-identified-as-key-to-chemotherapy-resistance-in-cancer-cells/

Paper DOI - https://doi.org/10.18632/oncotarget.28720

Correspondence to - Dindial Ramotar - dramotar@hbku.edu.qa

Video short - https://www.youtube.com/watch?v=suOhF7mPlNQ

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Keywords - cancer, redox signaling, homologous recombination, protein interaction, cell cycle, protein modification

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PRDX1 Identified as Key to Chemotherapy Resistance in Cancer Cells

BUFFALO, NY — September 23, 2025 — A new #research paper was #published in Volume 17, Issue 8 of Aging-US on August 7, 2025, titled “Senescent cell heterogeneity and responses to senolytic treatment are related to cell cycle status during senescence induction.”

This study, led by first authors Francesco Neri and Shuyuan Zheng, together with corresponding authors Denis Wirtz, Pei-Hsun Wu, and Birgit Schilling from the Buck Institute for Research on Aging, the USC Leonard Davis School of Gerontology, and Johns Hopkins University, reveals that not all aging cells behave the same. The researchers identified key differences between senescent cell subtypes that may influence how well they respond to senolytic drugs. These findings could help guide the development of more effective therapies for age-related diseases.

Senescent cells are aged or damaged cells that stop dividing and accumulate in tissues over time. While they play a role in wound healing and protecting against cancer early in life, they can drive chronic inflammation and tissue decline with age. Researchers are exploring ways to selectively remove these cells using senolytic drugs. However, the large variety of senescent cell types has made it difficult to design treatments that work for all of them. This study aimed to better understand the functional differences among senescent cell subpopulations.

Using high-resolution imaging, the team analyzed thousands of human endothelial and fibroblast cells growing in the lab. They observed that cells that exited the cell cycle (stopped dividing) in a later phase showed stronger signs of senescence and were more sensitive to senolytic treatment. These cells also produced more IL-6, a molecule associated with inflammation. The findings suggest that DNA content, which varies depending on the cell cycle phase, plays an important role in how aging cells function and how they respond to drugs.

“We found that G2-arrested senescent cells feature higher senescence marker expression than G1-arrested senescent cells.”

This is the first clear evidence that senescent cells do not all respond equally to treatment. The results suggest that future senolytic therapies could be more successful if they are designed to target specific subtypes of senescent cells, especially those with greater inflammatory potential.

While this research was conducted in laboratory cell cultures, it provides a foundation for studying how these findings apply to living tissues. Future work will examine whether similar patterns occur in the body and how this knowledge could lead to more precise and effective treatments for age-related conditions. Understanding the diversity of aging cells is key to developing therapies that are both safer and more targeted.

DOI - https://doi.org/10.18632/aging.206299

Corresponding authors - Denis Wirtz — wirtz@jhu.edu, Pei-Hsun Wu — pwu@jhu.edu, and Birgit Schilling — bschilling@buckinstitute.org

Abstract video - https://www.youtube.com/watch?v=x8bhKEFLzqA

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Keywords - aging, cellular senescence, imaging, heterogeneity, senolytics, cell cycle

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Aging-US

How Cell Cycle Status Affects Aging Cell Response to Senolytic Drugs

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Oncotarget is now indexed by MEDLINE, PubMed and PMC/PubMed.

Read about the Oncotarget Scientific Integrity Process: https://www.oncotarget.com/scientific_integrity/

Aging-US is dedicated to advancing our understanding of the biological mechanisms that drive aging and the development of age-related diseases. Our mission is to serve as a platform for high-quality research that uncovers the cellular, molecular, and systemic processes underlying aging, and translates these insights into strategies to extend healthspan and delay the onset of chronic disease.

Read about the Aging (Aging-US) Scientific Integrity Process: https://aging-us.com/scientific-integrity

New tracks tagged #cellcycle