Revolutionizing Pediatric Oncology: New Combination Therapy for Hepatoblastoma Shows Promise

In the realm of pediatric oncology, hepatoblastoma (HB), the most common liver cancer in children, has been steadily increasing worldwide over the past decade. However, a ray of hope has emerged from a team of researchers at Baylor College of Medicine. They have developed a novel combination therapy for HB, which has shown promising results in preclinical trials and offers potential for more effective treatment regimens.

Combination Therapy: A Novel Approach

The novel therapy, known as VIP therapy, combines an inhibitor of the enzyme histone deacetylase (HDAC) with existing chemotherapy drugs. Most notably, the therapy integrates an HDAC inhibitor called panobinostat with vincristine and irinotecan. This strategic combination has demonstrated significant reductions in tumor volume and alpha fetoprotein levels in high-risk, relapsed, and treatment-resistant HB within just one week of therapy. The previously untreatable cases are now seeing a glimmer of hope with this breakthrough.

Unveiling the Success in Animal Models

The researchers conducted their studies on aggressive animal models of HB that closely match human tumors. They found significant decreases in tumor volume and tumor marker levels following a week of the VIP therapy. Not only does this suggest the effectiveness of the new treatment strategy, but it also provides a foundation for future research into refining this therapeutic strategy for HB and potentially other cancers.

Role of Nur77 and Wnt β Catenin in HB

Additional research has shed light on the role of the orphan nuclear receptor Nur77 in HB. Nur77, also known as TR3 or NGFI-B, is encoded by the immediate early gene Nr4a1 and is an important regulator in cancer progression in various cancer types. Studies have found that Nur77 is downregulated in HB tumors and its interaction with β catenin accounts for the malignant progression of HB. Consequently, the combination of Nur77 agonist Csn B and cisplatin has been found to enhance the therapeutic effect of cisplatin on HB tumors, providing a new targeted therapy for the clinical treatment of HB patients.

Moreover, the Wnt β catenin pathway plays a critical role in liver biology and tumorigenesis. Abnormalities in this pathway promote the development and progression of hepatocellular carcinoma (HCC) and HB. Understanding the molecular basis of Wnt β catenin signaling and its characteristic changes due to abnormal activation is crucial for the development of future therapeutic agents.

Looking Ahead: Optimistic Future for HB Treatment

The development of the VIP therapy by Baylor College of Medicine marks a significant breakthrough in the treatment of HB. While the therapy has shown promising results in preclinical trials, further research is needed to validate these findings in clinical trials. If successful, this innovative combination therapy could revolutionize the treatment of HB, providing new hope for patients with currently untreatable high-risk, relapsed, or refractory HB.