Novel therapeutic strategies for cervical cancer:

co-targeting key molecular pathways

 

Cervical cancer remains a major cause of cancer-related mortality in women worldwide, with 604,000 new cases and 342,000 deaths reported in 2020. It is the fourth most common cancer in women globally. In India, nearly 100,000 new cases and 60,000 deaths occur annually. Persistent infection with high-risk human papillomavirus (HPV) genotypes, especially HPV 16 and 18, is the leading risk factor. About 55% of cases are diagnosed at an advanced stage, resulting in a 5-year survival rate of 66% in developing countries. Standard therapies include brachytherapy, chemotherapy (e.g., cisplatin, gemcitabine, paclitaxel, and topotecan), and targeted agents (e.g., bevacizumab, pembrolizumab). Despite these treatments, 15-61% of patients relapse within two years.

 

At the molecular level, key signaling pathways involved in cervical cancer include the PI3K/AKT/mTOR pathway, receptor tyrosine kinase pathway, and chromatin modification pathway. Receptor tyrosine kinase (RTK) pathways are significant oncogenic drivers and therapeutic targets. In a study involving next-generation sequencing of 99 cervical cancer patients, novel RTK pathways were found to be deregulated. Evidence suggests cooperativity among RTK pathways in driving cell growth and survival. Combining inhibitors targeting these pathways showed synergistic effects in other cancers. An orthotopic xenograft mouse model developed in NOD-SCID mice was used to investigate these combinatorial effects, highlighting the importance of targeting multiple pathways to overcome resistance and improve clinical outcomes.

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