INTERNATIONAL CONGRESS OF
CancerGenetics
Viral Vectors for Delivering p53 in Ovarian Cancer
-
Fereshteh Arefi,1,*
1. Biology Department, Faculty of Biosciences, Tehran North Branch, Islamic Azad University, Tehran, Iran
- Introduction: Ovarian cancer (OC) is a complex and varied disease that disproportionately affects women. It ranks as the seventh most common cancer worldwide, with over 238,000 new cases diagnosed annually. Developed countries see a particularly high burden, where it becomes the second most common gynecological cancer and often proves fatal. The key takeaway is that ovarian cancer isn't a single disease, but rather a group of different subtypes. These subtypes can vary greatly in their behavior. Some, like Type I tumors, grow slowly and stay confined to the ovary for extended periods. Others, like the aggressive Type II tumors, particularly high-grade serous carcinoma, spread rapidly and pose a significant threat from the outset. Ovarian cancer, especially the aggressive HGSOC, continues to be a major threat. Although overall survival rates have improved, HGSOC remains stubbornly difficult to treat, with a low 5-year survival rate. Diagnosing it late and confusing symptoms make it worse. Even the origin of the cancer itself is unclear, hindering efforts to develop effective treatments. There's a glimmer of hope for HGSOC despite the difficulties. A treatment called gene therapy uses tiny carriers to deliver healthy copies of a critical gene (p53) directly into cancer cells. This gene normally controls cell growth, but in HGSOC it's broken. By introducing a working copy, gene therapy has the potential to fix these cells and make them control their own growth again. However, there are challenges that need to be overcome before this approach can be widely used to fight ovarian cancer.
- Methods: Researchers explored delivering functional wild-type p53 (WT p53) genes to overcome frequent p53 mutations in ovarian cancer. However, finding an effective delivery system proved challenging. Viral vectors were initially favored due to efficient gene transfer. Adenoviral vectors (like Gendicine, Advexin, SCH-58500) were modified to carry WT p53 genes and lacked the ability to reproduce inside cancer cells for safety.
- Results: Despite initial mixed results from early attempts to replace dysfunctional p53 genes using adenovirus delivery (such as Gendicine, Advexin, and SCH-58500), the underlying strategy remains promising. Challenges posed by existing p53 mutations and the body’s immune response to the virus hindered those initial trials. However, researchers are actively exploring novel approaches to rejuvenate p53-based therapies. One exciting avenue involves creating improved p53 genes (such as p53-Bad and p53-CC) that could bypass existing mutations and overcome previous limitations. Additionally, advancements in delivery methods—such as nanoparticles and modified viruses—aim for more precise targeting of cancer cells with fewer side effects. Combining p53 therapy with other modalities, like immunotherapy, holds the potential for a comprehensive attack on ovarian cancer. Despite ongoing challenges related to the variety of p53 mutations, efficient delivery, and reliable disease markers, the relentless pursuit of enhanced p53 genes and deeper insights into ovarian cancer subtypes offers hope for the future of treatment.
- Conclusion: Ovarian cancer remains a significant health concern for women despite advancements in treatment. High-grade serous ovarian carcinoma (HGSOC), the most common and lethal subtype, presents challenges due to late-stage diagnosis and limited treatment efficacy. Viral vectors, such as adenoviruses (AdV) and adeno-associated viruses (AAV), have emerged as promising tools for delivering the tumor suppressor gene p53 directly into cancer cells of patients with ovarian cancer. Despite their potential, significant hurdles hinder the widespread application of viral vectors for p53 delivery in ovarian cancer treatment. Therefore, overcoming limitations related to delivery efficiency, tumor penetration, and off-target effects is crucial for their successful clinical application. Continued research in vector engineering and delivery methods holds promise for the development of effective p53 gene therapy for ovarian cancer.
- Keywords: Ovarian cancer, HGSOC, p53 gene, Gene delivery, Viral vectors
