Epigenetic Therapeutics in Osteosarcoma: Combining Histone Deacetylase Inhibitors with Genetic Targeting Strategies abstract
Osteosarcoma represents the most common primary malignant bone tumor with a high propensity for metastasis and poor response to conventional therapies. The annual estimated global incidence for osteosarcoma is about 3-5 cases per million, most frequently diagnosed in people aged 10 to 20 years. Despite improvement in treatment, including neoadjuvant chemotherapy, the prognosis remains poor and may fall below 20% for people with metastatic diseases. This constitutes an imperative need for novel treatment modalities directed against its molecular heterogeneity. Thus, this review discusses the rationale behind the use of epigenetic therapies in combination with genetic targeting approaches as a potential strategy to increase treatment efficiency against osteosarcoma. Methods: The review assesses recent progress in the integration of epigenetic and genetic approaches, particularly histone deacetylase inhibitors combined with genetic targeting techniques in osteosarcoma treatment. The study also considers how these epigenetic processes, including DNA methylation and histone modifications, may be used as part of therapeutic intervention. Results: The combination of HDAC inhibitors with genetic targeting strategies has revealed promising results in preclinical osteosarcoma models. Epigenetic therapies, especially HDAC inhibitors, have shown promise in preclinical osteosarcoma models by regulating oncogenic signaling pathways, promoting apoptosis, and enhancing chemotherapy sensitivity. HDAC-modulated chromatin structure and gene expression were leading to the reactivation of tumor suppressor genes. Coupled with
CRISPR-Cas9 system, RNA interference, and other gene-editing technologies, which offer precise methods for disrupting key oncogenes, these therapies can overcome drug resistance and improve the sensitivity of tumor cells to treatment. Conclusion: The combination of epigenetic and genetic therapies holds considerable potential to develop novel strategies for osteosarcoma. By targeting the underlying epigenetic and genetic drivers of the disease, such combined approaches reflect a promising pathway toward novel drug discovery and the development of personalized therapies that might improve patient outcomes by reducing metastasis and resistance to treatment.