Posted on 07/14/2025 12:38:53 PM PDT by Red Badger
Ovarian cancer cells dividing. (Credit: ecancer)
In A Nutshell
High-throughput drug screening identified rigosertib as highly selective for ovarian cancer cells.
Alone, rigosertib shuts down one survival pathway but triggers compensatory activation of another.
Combining rigosertib with PI3K/mTOR inhibitors prevents this resistance and shrinks tumors in mice.
Human trials are needed to confirm safety and effectiveness before clinical use.
==================================================================
NEW YORK — Scientists have identified a potentially game-changing treatment approach for ovarian cancer, one of the deadliest forms of the disease that kills roughly 12,740 American women each year. The breakthrough involves pairing an existing drug called rigosertib with medications that target specific cellular pathways, creating a one-two punch that appears to be far more effective than current treatments.
The research, published in Cell Reports Medicine, could offer new hope for patients facing a cancer with an 80% recurrence rate. Unlike many cancers that have clear genetic targets, ovarian cancer has proven notoriously difficult to treat because it doesn’t follow predictable patterns. Most patients initially respond to chemotherapy, only to see their cancer return within 18 months – often more aggressive and resistant than before.
Rigosertib, originally developed for blood cancers, works differently than traditional chemotherapy. Instead of broadly attacking rapidly dividing cells, it specifically disrupts the communication networks that cancer cells use to survive and multiply.
Drug Shows Selective Activity Against Ovarian Cancer
Rigosertib belongs to a class of medications called RAS mimetics, which essentially trick cancer cells by impersonating important cellular signals. RAS proteins are molecular switches that normally control when cells should grow and divide. When these switches get stuck in the “on” position due to cancer, cells multiply uncontrollably. Rigosertib works by blocking these faulty switches, particularly targeting two crucial survival pathways called MAPK and PI3K.
The research team, led by senior author Dr. Benjamin Hopkins at Weill Cornell Medicine, discovered that rigosertib showed remarkable selectivity for ovarian cancer cells compared to other cancer types. In laboratory tests across 32 different cell lines representing 11 types of cancer, ovarian cancer cells were consistently the most sensitive to rigosertib treatment.
Their systematic screening approach revealed this unexpected specificity, identifying rigosertib as particularly effective against ovarian cancer among the 117 compounds tested.
Why Single Drugs Fall Short
However, the scientists discovered a significant challenge: when cancer cells were treated with rigosertib alone, they activated backup survival systems. Cancer cells found alternative routes to stay alive by ramping up another pathway called PI3K/mTOR.
This adaptive response is a common problem in cancer treatment. Tumors are remarkably resourceful, often developing workarounds when faced with a single therapeutic approach. The research showed that while rigosertib successfully shut down one survival pathway, it inadvertently strengthened another, potentially limiting its effectiveness as a standalone treatment.
Combination Therapy Shows Superior Results
The breakthrough came when researchers tested rigosertib in combination with drugs that block the PI3K/mTOR pathway. Two drugs in particular – taselisib and buparlisib – showed remarkable synergy with rigosertib. When used together, they prevented cancer cells from activating their backup survival systems.
The combination approach was tested across multiple ovarian cancer cell lines and tissue samples from actual patients. These patient-derived samples, obtained from the National Cancer Institute’s repository, maintain the complex characteristics of real tumors, making them more realistic testing grounds than traditional cell lines.
Animal studies using laboratory mice with transplanted human ovarian tumors showed encouraging results. Animals treated with the rigosertib-taselisib combination had significantly smaller tumors compared to those receiving either drug alone or standard chemotherapy with cisplatin. Importantly, the mice maintained stable body weights throughout the study, and examination of major organs revealed no signs of toxicity.
Exploiting Cancer’s Vulnerabilities
The research team didn’t randomly test drug combinations. They first analyzed data from The Cancer Genome Atlas, a comprehensive database of tumor genetics, to understand how ovarian cancers differ from other types. They found that virtually all ovarian tumors (99%) have alterations in the MAPK and PI3K pathways that rigosertib targets.
This finding helps explain rigosertib’s selectivity for ovarian cancer. The drug appears to exploit vulnerabilities that are nearly universal in this cancer type but less common in others. The researchers also created detailed maps of protein activity that revealed ovarian tumors have hyperactive survival signaling compared to normal tissue.
While these results are promising, significant hurdles remain before this combination therapy might reach patients. The current research was conducted entirely in laboratory settings and animal models. Human clinical trials will be necessary to determine whether the combination is safe and effective in actual patients.
The researchers acknowledge several limitations. The animal studies used relatively small sample sizes and short treatment periods. The models also don’t capture the full complexity of advanced ovarian cancer, particularly the metastatic spread that makes this disease so deadly.
Despite these limitations, the research provides a strong scientific foundation for moving forward. For the thousands of women diagnosed with ovarian cancer each year, this research offers something that has been in short supply: a scientifically grounded reason for hope.
Disclaimer: This article summarizes findings from preclinical research published in Cell Reports Medicine. The results are based on laboratory and animal studies. No claims are made about safety or effectiveness in humans until clinical trials are conducted. Always consult a qualified medical professional for personalized medical advice.
Paper Summary
Methodology
The researchers conducted high-throughput drug screening using an automated platform to test 117 compounds across 32 cancer cell lines from 11 different tumor types. They specifically focused on seven genetically diverse ovarian cancer cell lines and used additional patient-derived organoids from three ovarian cancer patients obtained from the National Cancer Institute’s repository. The team employed combination drug screening, western blot analysis to measure protein activity, and mouse xenograft studies where human ovarian cancer cells were implanted in laboratory mice. The mice were then treated with various drug combinations to assess tumor growth and treatment tolerability.
Results
Rigosertib demonstrated selective activity against ovarian cancer cells compared to other cancer types. However, when used alone, it triggered compensatory activation of the PI3K/mTOR survival pathway. Combination treatment with PI3K inhibitors (taselisib and buparlisib) or mTOR inhibitors showed synergistic effects, with Bliss synergy scores indicating meaningful therapeutic benefit. In mouse studies, the rigosertib-taselisib combination significantly reduced tumor growth compared to single agents or standard chemotherapy, while maintaining acceptable safety profiles with no significant toxicity observed.
Limitations
The study was conducted entirely in laboratory settings using cell lines and animal models, which may not fully represent the complexity of human ovarian cancer. The animal studies used relatively small sample sizes and short treatment periods. The research did not include metastatic models, which would better represent the patient population most likely to receive this treatment. Additionally, the study focused on a limited number of drug combinations and did not explore optimal dosing strategies or potential resistance mechanisms.
Funding and Disclosures
This research was supported by grant CA230384. Dr. Hopkins disclosed being a founder and consultant for Faeth Therapeutics, and his laboratory received support from Faeth Therapeutics (including the sapanisertib used in the study), as well as Jazz Pharmaceuticals and Novartis for unrelated projects. Dr. Elemento reported owning equity in Owkin and Volastra Therapeutics, which were unrelated to this research.
Publication Information
The study was published in Cell Reports Medicine, Volume 6, Article 102218, on July 15, 2025, by authors Shalini Nath, Benjamin Hopkins, Sally Claridge, Genesis Lara Granados, and colleagues from Weill Cornell Medicine and Icahn School of Medicine at Mount Sinai. The paper is available as an open access article under the CC BY-NC license and can be accessed at
https://doi.org/10.1016/j.xcrm.2025.102218.
|
Click here: to donate by Credit Card Or here: to donate by PayPal Or by mail to: Free Republic, LLC - PO Box 9771 - Fresno, CA 93794 Thank you very much and God bless you. |
Ping!......................
I hope this treatment works. Ovarian cancer is what ended the life of my beloved sister.
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.