Research Projects

5-fluorouracil (5-FU) is the primary chemotherapy drug for solid tumors, including colorectal cancer (CRC), but its toxic side effects have raised concerns about its use as an anticancer drug. Combinatorial drug regimens (FOLFIRI and FOLFLOX) have been attempted to overcome chemoresistance and achieve reoccurrence-free survival, but their response rate is poor due to their heterogeneous nature. To overcome these dose-dependent side effects, it is crucial to achieve antineoplastic characteristics with low dosages of individual drugs. Challenges in colorectal tumorigenesis include chronic inflammation and overexpression of cyclooxygenase-2 (COX-2). However, these NsAIDs can inhibit CRC cell growth without COX-2 expression, activating peroxisome proliferator activated receptor-γ (PPARγ). PPARγ can also be activated by synthetic antidiabetic thiazolidinediones (TZDs), which have demonstrated anti-tumor activities against various malignancies both in vivo and in vitro. This study aims to investigate whether PPARγ could serve as a prognostic marker for CRC and if combinations of current therapeutics and PPARγ agonists could lower the dosage required for cancer cell killings with limited adverse effects to normal cells. The findings of this novel hypothesis could help reposition the chemotherapeutic regimen against colorectal cancer, providing better anticancer efficcies and fewer adverse effects. In addition to in vitro and in vivo approaches, the study includes in silico screening of vital biomolecules as off-targets using bioinformatic tools like molecular docking. This would help identify the vital metabolic and signaling pathways involved in adverse effects likely caused by these drugs, benefiting future drug discovery studies.