Background: Oral Squamous Cell Carcinoma (OSCC) is a major sub-type of oral cancer
that shares 90% proportion of oral cavity cancers. It is declared as the sixth most frequent cancer
among all cancer types throughout the world. Higher morbidity in Asian countries is reported due to
frequent use of Smokeless Tobacco (SLT) products besides exposure to other risk factors. Hyperactivation
of epidermal growth factor receptors is a molecular event in many solid tumors including
oral cancer making them potential therapeutic targets.
Objective: Current study was designed to explore the effect of varlitinib, a pan-HER inhibitor, on oral
cancer cell line. We investigated key regulatory genes in downstream pathway in response to drug
treatment. Furthermore, we also examined expression profile of these genes in malignant and healthy
Methods: Gene expression pattern in drug treated and untreated cancer cell line along with OSCC tumor
samples (n=45) and adjacent normal tissues was studied using real time PCR.
Results: In response to varlitinib treatment, significant suppression of oncogenes (IGF1R, MAPK1,
SFN and CDK2) was observed. Interestingly, mRNA expression level of CDKN1A and Akt1 was found
to be the opposite of what was expected. In case of malignant tissue, over expression of oncogenes
(IGF1R, Akt1, MAPK1, SFN and CDK2) with simultaneous down expression of tumor suppressor
genes (Tp53 and CDKN1A) was noted. STRING analysis indicated a strong association among differentially
expressed genes suggesting their combined role in carcinogenesis.
Conclusion: In summary, our results indicate that varlitinib can be considered as a potential therapeutic
agent in oral cancer due to its antitumor potential.