Posted on 09/08/2024 8:24:39 PM PDT by ConservativeMind
Researchers have identified a promising new combination therapy for metastatic colorectal cancer that enhances the effectiveness of existing treatment while reducing harmful side effects.
The study focused on regorafenib, a drug that modestly improves survival in mCRC patients but often leads to severe toxicities. By pairing regorafenib with a dual JAK/HDAC inhibitor at low doses, the researchers were able to significantly boost the drug's anticancer activity.
For patients with metastatic disease, treatment options are limited and the prognosis is often poor. Regorafenib, a multiple-kinase inhibitor, is one of the few drugs available for these patients; but its use is hampered by significant toxicity, limiting its clinical benefit.
The research team conducted a series of experiments using colorectal cancer cell lines, patient-derived xenografts and mouse models to test the efficacy of the combination therapy.
They examined the effects of the combination on cell viability, cell cycle progression, apoptosis (programmed cell death) and molecular signaling pathways. Researchers explored how the treatment influenced the immune response to the tumors.
The combination therapy outperformed regorafenib alone across several metrics. It significantly reduced tumor cell viability, induced cell cycle arrest at the G0-G1 phase and promoted apoptosis. The combination also inhibited key molecular pathways involved in cancer growth, including those regulated by JAKs, STAT3 and EGFR. Importantly, the treatment enhanced the immune system's ability to target the tumor.
In animal models, the combination therapy led to a significant reduction in tumor growth and metastasis. Pharmacokinetic studies further revealed that the combination increased the bioavailability of regorafenib, meaning more of the drug was available to exert its effects, potentially allowing for lower doses and reducing toxicity.
The study's findings suggest that combining regorafenib with a dual JAK/HDAC inhibitor could be a more effective and safer approach to treating metastatic colorectal cancer.
(Excerpt) Read more at medicalxpress.com ...
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