Fadraciclib Shows Efficacy in Colorectal Cancer Models at 2024 ASCO

Cyclacel Pharmaceuticals, a biopharmaceutical company focusing on innovative cancer treatments, recently announced promising preclinical results for their CDK2/9 inhibitor, fadraciclib, as a potential treatment for metastatic colorectal cancer (CRC). The findings were presented by independent researchers at the American Society of Clinical Oncology (ASCO) Annual Meeting, highlighting fadraciclib’s ability to significantly inhibit tumor growth and induce a novel cancer-specific mechanism known as anaphase catastrophe.

Study Overview

Led by Dr. David S. Hsu from Duke University, the study aimed to evaluate the efficacy of fadraciclib in treating CRC. The research team treated 18 patient-derived organoids (PDOs) from individuals with primary or metastatic CRC with various therapies, including standard chemotherapy, palbociclib (a CDK4/6 inhibitor), and fadraciclib. The results demonstrated that fadraciclib was more effective in reducing tumor growth compared to the other treatments. Additionally, three patient-derived xenografts (PDXs) were created for in vivo validation, confirming the inhibitor's effectiveness when administered orally.

Mechanism and Results

The study revealed that fadraciclib effectively inhibited both CDK2 and CDK9, causing significant tumor growth reduction and apoptosis in the treated CRC models. This was confirmed through various techniques like western blotting, flow cytometry, and immunofluorescence staining. Notably, fadraciclib induced anaphase catastrophe, a process that disrupts mitosis in cancer cells, leading to cell death. This mechanism targets aneuploid cancer cells, which possess an abnormal number of chromosomes, making it a novel approach in cancer treatment.

Broader Implications

Spiro Rombotis, President and CEO of Cyclacel Pharmaceuticals, emphasized that these findings support fadraciclib’s potential across multiple tumor types. The company is currently conducting the proof-of-concept phase of the 065-101 study, targeting patients with specific tumor suppressor gene alterations and T-cell lymphoma. Initial results from this study are expected in the latter half of 2024.

About Colorectal Cancer and Cyclin-Dependent Kinases

Colorectal cancer is the third most prevalent cancer among adults in the United States, with limited treatment options available, especially for advanced stages. The heterogeneous nature of CRC necessitates the exploration of new therapeutic targets. Cyclin-dependent kinases (CDKs) play a crucial role in cell cycle control and transcription regulation. Dysregulated CDKs are often associated with uncontrolled cell proliferation and cancer progression.

Fadraciclib’s Potential

Fadraciclib is a highly selective inhibitor of CDK2 and CDK9, demonstrating significant anti-cancer activity at sub-micromolar concentrations. It induces cancer cell death via anaphase catastrophe, a mechanism not exploited by existing treatments. Previous studies have shown promising single-agent activity in treating various cancers, including endometrial, lung, ovarian, and pancreatic cancers, as well as T-cell lymphoma.

Ongoing Clinical Trials

Currently, fadraciclib is being evaluated in a Phase 1/2 clinical trial (065-101 study) involving patients with advanced solid tumors and lymphoma. The study has enrolled 47 patients thus far and aims to further assess the drug’s safety and efficacy. Specific cohorts are being evaluated based on histology and genomic profiles, including those with CDKN2A/CDKN2B alterations and advanced T-cell lymphoma. These genetic alterations are prevalent in several cancer types, underscoring the broad potential of fadraciclib.

Conclusion

Cyclacel Pharmaceuticals is at the forefront of developing innovative cancer treatments, with fadraciclib showing promising preclinical results for metastatic colorectal cancer. The company’s strategy involves leveraging their pipeline of novel drug candidates to address unmet medical needs in oncology and hematology. As the clinical trials progress, the medical community eagerly awaits further data on fadraciclib’s efficacy and safety in treating various cancer types.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!