Latest news with #CDKN2A
Newsweek
04-08-2025
- Health
- Newsweek
Hard-to-Treat Cancers Respond to New Therapy
Based on facts, either observed and verified firsthand by the reporter, or reported and verified from knowledgeable sources. Newsweek AI is in beta. Translations may contain inaccuracies—please refer to the original content. A promising new combination therapy is offering new hope for patients with hard-to-treat cancers. This is thanks to scientists at the Fralin Biomedical Research Institute in Virginia who have identified a potential target for experimental drugs that block PRMT5—a naturally occurring enzyme some tumors rely more on for survival. The study could help guide the development of new therapies for some treatment-resistant lung, brain and pancreatic cancers, according to the researchers. "Using genetic screening, we found a new drug combination that seemingly works," said paper author and cancer biologist professor Kathleen Mulvaney in a statement. A 3D illustration of DNA and cancer cells. A 3D illustration of DNA and cancer cancer is by far the most fatal type of cancer in the US, accounting for about one in five of all cancer deaths. Meanwhile, the five-year survival rate is less than 15 percent for pancreatic cancer patients (although this can vary depending on the stage of cancer) and even lower for glioblastoma, a fast growing type of brain tumor. While treatment options are available, the need for new types is also clear. "With one drug alone, tumors can become resistant really quickly," Mulvaney said. "In all cases, the combination is better at killing than the single agents." The findings suggest the PRMT5 inhibitor could be a powerful new approach for these hard-to-treat cancers. Many of these types of solid tumors share a genetic trait—they lack the genes CDKN2A and MTAP. Both of these are important as they suppress tumors and help to regulate cell growth. Without them, the cancers become dependent on PRMT5 and potentially vulnerable to drugs that lock the enzyme. "It's very difficult to make a drug against the absence of something, so the discovery that PRMT5 is a target we can make a drug against is very exciting to treat CDKN2A/MTAP deleted cancers," Mulvaney told Newsweek. "A new revolutionary class of inhibitors, referred to as MTA-cooperative PRMT5 inhibitors, has shown promising results in ongoing early phase clinical trials," the researchers also explained in the paper. "Nonetheless, effective cancer treatment typically requires therapeutic combinations to improve response rates and defeat emergent resistant clones. Thus, we sought to determine whether perturbation [disrupting or altering] of other pathways could improve the efficacy of MTA-cooperative PRMT5 inhibitors." Doctor showing smiling patient a lung x-ray scan image. Doctor showing smiling patient a lung x-ray scan image. stefanamer/Getty Images To inform their research, the scientists analyzed genetic data from thousands of cancer patients available through the cBioPortal, an open-access resource. They applied a gene-editing technology called CRISPR to look at biological pathways across a range of samples to determine which genes make cancer cells more vulnerable to PRMT5 inhibitors and which combinations could improve response and long-term outcomes. Mulvaney estimates that around five percent of all cancer patients—some 80,000–100,000 per year in the US—could benefit from the newly identified therapies. Using PRMT5 inhibitors with drugs that block a communication system that tells cancer cells when to grow, divide or shut down the—'MAP kinase pathway'—the scientists identified potential treatments for clinical trials. "We also discovered a number of genes that interact with PRMT5 signaling in cancer that were not previously known," said Mulvaney. As well as hopefully helping to lead to better lung, brain and pancreatic treatments, the therapy shows promise for other types of cancer. This includes melanoma—the most dangerous type of skin cancer—and mesothelioma—mainly affecting the lining of the lungs, though can also affect the lining of the stomach, heart of testicles. In both animal models and cell cultures derived from patient tissue, lab members saw success after testing potential therapies. Mulvaney explained that in the lung cancer models, for example, 75 percent of mice ended up with no detectable tumors after treatment. These responses were stable after drug withdrawal. "In all cases, the combination is better at killing cancer cells than the single agents," she said. "Only the combinations led to complete regressions." Mulvaney explained further, "We've only tested dosing concurrently in preclinical models. It will be interesting to test whether the drug dosing order matters e.g., if we can treat with one compound before adding the other for further benefit or whether concurrent dosing is better." Could there be increased side effects from the new therapy? "In the preclinical mouse models, the combination dosing was well tolerated; no weight loss was detected in the mice. It will be important to monitor potential side effects of the combination in the clinical trials." The researchers concluded in the paper, "Overall, this study identifies therapeutic combinations with MTA-cooperative PRMT5 inhibitors that may offer significant benefit to patients." Do you have a tip on a health story that Newsweek should be covering? Do you have a question about cancer? Let us know via health@ Reference Knoll, N., Masser, S., Bordas, B., Ebright, R. Y., Li, G., Kesar, D., Destefanis, E., Kania, N., Rodriguez, D. J., Jen, J., Zagar, S. E., Mensah, C., Chen, Z., Moffitt, S. J., Enakireru, E. M., He, Y., Feng, B., Chokshi, M. K., Jin, C. Y., ... Mulvaney, K. M. (2025). CRISPR-Drug Combinatorial Screening Identifies Effective Combination Treatments for MTAP-deleted Cancer. Cancer Research.
Business Wire
27-05-2025
- Health
- Business Wire
Preclinical Data on Circle Pharma's CID-078 Featured in Poster Presentation at Advances in Neuroblastoma Research Meeting
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Circle Pharma, a clinical-stage biopharmaceutical company advancing macrocycle therapeutics for difficult-to-treat cancers, today announced the presentation of preclinical data on CID-078 at the Advances in Neuroblastoma Research (ANR) Meeting in Washington, D.C., May 25-28, 2025. The data, which explore the therapeutic potential of CID-078 in neuroblastoma (NB), were presented in a poster entitled: 'Cyclin A/B-RxL Inhibition as a Novel Therapeutic Strategy in Neuroblastoma' Dylan M.M. Jongerius et al. Poster #P010 The poster highlights the work of researchers from the Princess Máxima Center for Pediatric Oncology (Utrecht, the Netherlands), the Hopp Children's Cancer Center Heidelberg (KiTZ) (Heidelberg, Germany), and Circle Pharma, demonstrating the potent anti-tumor activity of CID-078 in preclinical neuroblastoma (NB) models. CID-078 is a first-in-class oral macrocycle cyclin A/B RxL inhibitor that selectively disrupts RxL-mediated interactions between cyclin A2/B1 and their substrates, a novel mechanism of action that targets cell cycle dysregulation in cancer. In neuroblastoma, where CDK-RB-E2F axis deregulation and oncogenic E2F activity are common, this mechanism is particularly relevant. Key Findings Presented: Potent Single agent CID-078 activity was observed across multiple neuroblastoma cell line models. Mechanism of action studies confirmed induction of DNA damage, G2/M arrest and the activation of the spindle assembly checkpoint (SAC). Deletion of CDKN2A sensitized cells to CID-078 suggesting CDKN2A status maybe be used as a potential patient stratification strategy. 'A greater understanding of the biology of neuroblastoma, the most common extra-cranial solid tumor diagnosed in children, has shown specific genomic alterations which deregulate the cell cycle leading to E2F activation,' said Michael C. Cox, PharmD, MHSc, BCOP, SVP and head of early development of Circle Pharma. 'Circle's collaboration with these two premier pediatric oncology research institutions has shown again the potential of our macrocycle platform to develop new therapies for historically challenging targets. The exciting CDKN2A deletion biomarker data, as well as the in vitro data in a pediatric tumor with a need for better treatments support our clinical development plans for CID-078.' The full poster is available here. About CID-078, Circle Pharma's Cyclin A/B RxL Inhibitor Program CID-078 is an orally bioavailable macrocycle with dual cyclin A and B RxL inhibitory activity that selectively targets tumor cells with oncogenic alterations that cause cell cycle dysregulation. In biochemical and cellular studies, Circle Pharma's cyclin A/B RxL inhibitors have been shown to potently and selectively disrupt the protein-to-protein interaction between cyclins A and B and their key substrates and modulators, including E2F (a substrate of cyclin A) and Myt1 (a modulator of cyclin B). Preclinical studies have demonstrated the ability of these cyclin A/B RxL inhibitors to cause single-agent tumor regressions in multiple in vivo models. A multi-center phase 1 clinical trial (NCT06577987) is currently enrolling patients. About Circle Pharma, Inc. South San Francisco-based Circle Pharma is a clinical-stage biopharmaceutical company harnessing the power of macrocycles to develop therapies for cancer and other serious illnesses. The company's proprietary MXMO™ platform overcomes key challenges in macrocycle drug development, enabling the creation of intrinsically cell-permeable and orally bioavailable therapies for historically undruggable targets. Circle Pharma's pipeline is focused on targeting cyclins, key regulators of the cell cycle that drive many cancers. Its lead program, CID-078, a cyclin A/B-RxL inhibitor, is in a Phase 1 clinical trial (NCT06577987) for patients with advanced solid tumors. To learn more about Circle Pharma, please visit
Yahoo
27-05-2025
- Business
- Yahoo
Preclinical Data on Circle Pharma's CID-078 Featured in Poster Presentation at Advances in Neuroblastoma Research Meeting
SOUTH SAN FRANCISCO, Calif., May 27, 2025--(BUSINESS WIRE)--Circle Pharma, a clinical-stage biopharmaceutical company advancing macrocycle therapeutics for difficult-to-treat cancers, today announced the presentation of preclinical data on CID-078 at the Advances in Neuroblastoma Research (ANR) Meeting in Washington, D.C., May 25-28, 2025. The data, which explore the therapeutic potential of CID-078 in neuroblastoma (NB), were presented in a poster entitled: "Cyclin A/B-RxL Inhibition as a Novel Therapeutic Strategy in Neuroblastoma"Dylan M.M. Jongerius et #P010 The poster highlights the work of researchers from the Princess Máxima Center for Pediatric Oncology (Utrecht, the Netherlands), the Hopp Children's Cancer Center Heidelberg (KiTZ) (Heidelberg, Germany), and Circle Pharma, demonstrating the potent anti-tumor activity of CID-078 in preclinical neuroblastoma (NB) models. CID-078 is a first-in-class oral macrocycle cyclin A/B RxL inhibitor that selectively disrupts RxL-mediated interactions between cyclin A2/B1 and their substrates, a novel mechanism of action that targets cell cycle dysregulation in cancer. In neuroblastoma, where CDK-RB-E2F axis deregulation and oncogenic E2F activity are common, this mechanism is particularly relevant. Key Findings Presented: Potent Single agent CID-078 activity was observed across multiple neuroblastoma cell line models. Mechanism of action studies confirmed induction of DNA damage, G2/M arrest and the activation of the spindle assembly checkpoint (SAC). Deletion of CDKN2A sensitized cells to CID-078 suggesting CDKN2A status maybe be used as a potential patient stratification strategy. "A greater understanding of the biology of neuroblastoma, the most common extra-cranial solid tumor diagnosed in children, has shown specific genomic alterations which deregulate the cell cycle leading to E2F activation," said Michael C. Cox, PharmD, MHSc, BCOP, SVP and head of early development of Circle Pharma. "Circle's collaboration with these two premier pediatric oncology research institutions has shown again the potential of our macrocycle platform to develop new therapies for historically challenging targets. The exciting CDKN2A deletion biomarker data, as well as the in vitro data in a pediatric tumor with a need for better treatments support our clinical development plans for CID-078." The full poster is available here. About CID-078, Circle Pharma's Cyclin A/B RxL Inhibitor Program CID-078 is an orally bioavailable macrocycle with dual cyclin A and B RxL inhibitory activity that selectively targets tumor cells with oncogenic alterations that cause cell cycle dysregulation. In biochemical and cellular studies, Circle Pharma's cyclin A/B RxL inhibitors have been shown to potently and selectively disrupt the protein-to-protein interaction between cyclins A and B and their key substrates and modulators, including E2F (a substrate of cyclin A) and Myt1 (a modulator of cyclin B). Preclinical studies have demonstrated the ability of these cyclin A/B RxL inhibitors to cause single-agent tumor regressions in multiple in vivo models. A multi-center phase 1 clinical trial (NCT06577987) is currently enrolling patients. About Circle Pharma, Inc. South San Francisco-based Circle Pharma is a clinical-stage biopharmaceutical company harnessing the power of macrocycles to develop therapies for cancer and other serious illnesses. The company's proprietary MXMO™ platform overcomes key challenges in macrocycle drug development, enabling the creation of intrinsically cell-permeable and orally bioavailable therapies for historically undruggable targets. Circle Pharma's pipeline is focused on targeting cyclins, key regulators of the cell cycle that drive many cancers. Its lead program, CID-078, a cyclin A/B-RxL inhibitor, is in a Phase 1 clinical trial (NCT06577987) for patients with advanced solid tumors. To learn more about Circle Pharma, please visit View source version on Contacts Media Contact:Roslyn Patterson Phone: 650.825.4099 Email: Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
