Characterization of therapeutically relevant alterations in cervical cancer using orthotopic mice models
Implementing Organization
Tata Memorial Centre Advanced Centre For Treatment, Research And Education In Cancer
Principal Investigator
Dr. Ashwin Babanrao Butle
Research And Education In Cancer, Delhi
Tata Memorial Centre Advanced Centre For Treatment
About
Cervical cancer is the second most common cancer in India and accounts for 25% of the world's incidence. Treatment options include brachytherapy and chemotherapy, but patients with metastasized disease have a median survival time of 8-13 months and a 5-year survival rate of 16.5%. To address this, researchers have conducted genomic profiling for mutations in 99 cervical cancer samples from Indian patients using NGS and other genotyping methods. The analysis identified several recurrent mutations in druggable genes such as PIK3CA, ERBB2, FGFR2, and others. These findings have the potential to transform treatment in cervical cancer. Preliminary in vitro data suggest a role of ERBB2 mutations in cervical cancer. The C33A cervical cancer cells, harboring ERBB2 alteration, were found to be sensitive to pan EGFR inhibitor BIBW-2998. However, subcutaneous xenografts developed in NOD-SCID mice failed to mimic human cervical cancer to address metastasis and invasion properties of cervical tumors. The present study proposes characterizing therapeutically relevant alterations in cervical cancer by developing a rare and intricate mouse model of cervical cancer by orthotopic transplantation of the tumor fragment directly to the cervix using luciferase tagged cervical cancer C33A cells and immortalized epithelial normal cells overexpressing mutant candidate genes.