Anticancer activity of a small molecule, tolfenamic acid: An emphasis on pancreatic cancer

Tolfenamic acid (TA) is a small molecule and nonsteroidal inflammatory drug. TA exhibited anticancer activity in preclinical studies in multiple cancer models. Its anticancer activity was first reported in pancreatic cancer cells and an animal tumor model in 2006. Since then, more than 60 articles have been published regarding TA’s anticancer activity in various cancers; however, one-third of these studies were related to pancreatic cancer. TA has been investigated for its anticancer activity. It was also explored in combination studies alongside radiation or investigational agents such as curcumin and mithramycin. It has been shown to act as a sensitizing agent to induce a response to irradiation in pancreatic cancer cells and tumor growth in mouse (orthotopic model model). The copper complex of TA (Cu-TA) was also investigated and was found to inhibit pancreatic cancer cell growth and tumor progression effectively in mouse models at a lower dose than TA. There is ample evidence to believe that the primary target for TA’s anticancer activity is mediated through specificity protein transcription factor 1. Some studies have proposed that either TA or Cu-TA could be inhibiting the expression of survivin, an antiapoptotic protein responsible for anticancer efficacy as a single agent or in combination. Microarray analysis using three pancreatic cancer cell lines demonstrated that TA modulates the pathways and networks that are mostly associated in cancer cell growth and progression, which further supports its use as an anticancer agent in pancreatic cancer. Overall, there is a large body of evidence supporting the efficacy of TA in cancer treatment in preclinical models with strong data using pancreatic cancer cells and mouse tumor models.