From Surviving Treatment to Preventing Recurrence: SiSP Research Reveals a New Strategy Against Ovarian Cancer
Congratulations to Dr. Sutthipun Suriya on His Latest Publication in Biomedicine & Pharmacotherapy
We are delighted to celebrate another exciting milestone from the Siriraj Center of Research Excellence for Systems Pharmacology (SiSP).
Congratulations to Dr. Sutthipun Suriya, who led the publication of our latest research as first author, under the supervision of Asst. Prof. Dr. Somponnat Sampattavanich. This work uncovers a previously underappreciated mechanism behind ovarian cancer recurrence and proposes a promising strategy to eliminate the cancer cells that survive modern targeted therapy.
Why Does Ovarian Cancer Come Back?
High-grade serous ovarian cancer (HGSOC) is the most aggressive and lethal form of ovarian cancer. Over the past decade, PARP inhibitors, such as olaparib, have transformed treatment for many patients, particularly those whose tumors carry defects in DNA repair pathways. These targeted therapies can produce remarkable clinical responses, yet many patients unfortunately experience disease recurrence months or years later.
For many years, researchers have searched for genetic mutations that explain why tumors become resistant to treatment. While genetic changes certainly contribute, they do not tell the whole story.
Our team asked a different question:
What if some cancer cells do not become resistant at all—but instead survive by temporarily "going to sleep"?
When Cancer Cells Choose to Sleep Instead of Die
Our study demonstrates that PARP inhibitors do more than simply kill cancer cells.
A small population of surviving cells enters a temporary dormant state, where they stop dividing but remain alive. During this process, many transform into enlarged polyploid giant cancer cells (PGCCs)—cells that appear inactive yet retain the remarkable ability to generate new daughter cells once treatment is withdrawn. These dormant cells therefore serve as a hidden reservoir that can repopulate the tumor and contribute to disease recurrence.
This finding changes the way we think about treatment resistance.
Rather than focusing exclusively on genetic resistance, we must also consider adaptive survival states, in which cancer cells effectively "wait out" therapy before reawakening.
Searching for the Dormant Cells' Achilles' Heel
To understand how these dormant cells survive, our team combined multiple cutting-edge technologies in systems biology, including:
Transcriptomics (RNA sequencing)
Proteomics (Reverse Phase Protein Array)
Computational drug prediction
High-content imaging
Functional drug screening
By following cancer cells throughout their entire journey—from drug-naïve, to therapy-induced dormancy, and finally to recovery after treatment withdrawal—we discovered a common vulnerability shared across different ovarian cancer models.
Despite their biological differences, dormant cancer cells all became highly dependent on maintaining their redox balance—their ability to control harmful reactive oxygen species (ROS).
This dependence represents an unexpected therapeutic opportunity.
An Unexpected Candidate: Disulfiram
One of the most exciting discoveries from this study was the identification of Disulfiram, a medication that has been safely prescribed for decades to treat alcohol dependence.
Our experiments showed that combining Disulfiram with PARP inhibitors:
disrupted the cancer cells' antioxidant defense,
increased oxidative stress (ROS),
enhanced DNA damage,
eliminated dormant polyploid giant cancer cells,
and dramatically reduced the ability of surviving cancer cells to regrow after treatment.
Importantly, these beneficial effects were observed across ovarian cancer models representing different levels of homologous recombination deficiency (HRD), suggesting that this therapeutic strategy may be broadly applicable rather than limited to a single molecular subtype.
Why This Matters
One of the greatest challenges in cancer treatment is not simply shrinking tumors—it is preventing them from returning.
Our findings suggest that future therapies should aim not only to destroy rapidly dividing cancer cells but also to eliminate the dormant cells that silently survive treatment and later fuel recurrence.
Because Disulfiram is already an approved medication with a well-established safety profile, repurposing it alongside PARP inhibitors could potentially accelerate future translational research. Although additional studies in animal models and clinical trials will be required before this strategy can be applied to patients, our work provides a strong mechanistic foundation for pursuing this promising therapeutic approach.
A Systems Pharmacology Success Story
This publication exemplifies SiSP's mission of integrating systems biology, quantitative pharmacology, multi-omics technologies, computational biology, and experimental validation to answer clinically important questions.
Rather than studying individual genes in isolation, we seek to understand how complex biological systems adapt during treatment—and how these adaptive mechanisms can be therapeutically exploited to improve patient outcomes.
Congratulations, Jack!
This publication represents years of dedication, perseverance, and scientific creativity.
We extend our heartfelt congratulations to Dr. Sutthipun "Jack" Suriya for leading this ambitious project from concept to publication. His work advances our understanding of ovarian cancer biology while opening exciting new directions for overcoming therapy resistance and preventing disease recurrence.
Congratulations also to all members of the research team and collaborators who contributed to this achievement. We look forward to seeing how these discoveries will shape the next generation of precision oncology research.
Reference
Suriya S., Jamnongsong S., Jamyuang C., Therasakvichya S., Sampattavanich S. PARP inhibition induces a redox-dependent dormant reservoir vulnerable to disulfiram in high-grade serous ovarian cancer.Biomedicine & Pharmacotherapy (2026). DOI: https://doi.org/10.1016/j.biopha.2026.119821
