Research Projects

In India, cervical cancer is the second most common cancer among women, contributing to 17% of the global burden. Incidence of cervical cancer is 96322 while 60078 deaths occur in India with 5-year survival rate of mere 46%. The common treatment line for cervical cancer patients includes brachytherapy and chemotherapy with cisplatin, gemcitabine and paclitaxel. After completion of treatment, 15-61% of the patients are presented with the metastatic disease within two years. However, common observation is that cancer cells frequently develop resistance to single-drug treatments. To counter this challenge, promising strategy involves utilizing combinatorial therapy– an approach that targets multiple pathways and has shown promising outcomes across various cancer types. we have done extensive NGS based analysis of 99 cervical adenocarcinoma and squamous carcinoma patient samples (previous work from the Dutt Laboratory, ACTREC, Navi-Mumbai). NGS based genomic analysis of Indian cervical cancer patients revealed notable genetic mutations in PIK3CA(14.6%), ARID1A(10.7%), CREBBP(10.7%), FAT4(19.6%), LRP1B(12.5%), ERBB2(7.2%) with many novel therapeutically targetable genetic alterations which were not reported to be significantly mutated in previous cervical cancer studies. FGFR2 was found to be novel significantly mutated gene (known oncogenic mutation K660E) in in adeno and squamous carcinoma Indian cervical cancer patient samples (Preliminary data). Orthotropic mouse models are the most relevant preclinical model to test the effect of therapeutic agents in terms of their effect on metastasis, tumorigenicity and pharmacological bioavailability. Therefore, we have developed in-house orthotopic mouse model in NOD-SCID using mice surgically engrafted xenograft tumors made from cervical cancer cell line C33A. Weekly bioluminescence imaging (BLI) of orthotopic xenografted mice shows gradual increase in BLI signal reveals tumor growth at the cervix. Also, we found metastasis in visceral organs like lungs, liver, kidneys, spleen and in local lumber periaortic local lymph nodes. After ensuring the faithful recapitulation of cervical cancer associated clinical features in our orthotopic cervical cancer model, we have investigated the effect of ERBB2 and FGFR2 overexpression on tumorigenicity (Preliminary data).. The work was funded by SERB-NPDF, File No: PDF/2021/003265. The proposed study is aiming with the assessment of effect of combinatorial treatment of FDA approved TKIs (BIBW2992 for ERBB2 and BGJ398 for FGFR2) by using previously established preclinical orthotopic cervical cancer mouse model. The results of this study will have the potential to stimulate additional research efforts and facilitate the advancement of targeted treatments for cervical cancer.