Oral cancer patients at an advanced stage show poor clinical outcomes. Cancer stem cells (CSCs) within these tumors are able to evade chemo-radiotherapy, leading to the recurrence of disease post-treatment. Our group is investigating the mechanisms involved in the maintenance of CSCs. Whole transcriptome profile was carried out for the CSCs isolated from patient samples which revealed a distinct metabolic rewiring hinting towards new avenues to target CSCs. In order to validate and get a mechanistic insight we have established 6 novel oral cancer cell lines in our lab, from advanced-stage treatment naïve oral cancer patient tumors, including three cell lines each from carcinoma of buccal mucosa and oral tongue. These primary cell lines are utilized for in vitro assays as well as for orthotopic model studies. Additionally, chemo-resistant cell line models for multiple chemotherapeutic agents such as Cisplatin, Docetaxel, 5-Fluorouracil are also being used to study the molecular mechanism underlying chemoresistance