Key result
Combining gefitinib and DIM-C maximally inhibits in vivo bladder tumor growth versus monotherapy or control.
Why the study?
The crosstalk between EGFR and PPARγ signalling pathways and their combined therapeutic potential in bladder cancer were investigated due to recent evidence implicating PPARγ in anticancer therapy.
Does the combination of gefitinib and DIM-C inhibit growth in bladder cancer models compared to monotherapy?
Does the combination of gefitinib and DIM-C inhibit growth in bladder cancer models compared to monotherapy?
The combination of an EGFR inhibitor and a PPARγ agonist demonstrates synergistic inhibition of bladder cancer growth in preclinical models.
Supports dual EGFR-PPARγ targeting in bladder cancer models; leaves open clinical translation.
BACKGROUND: Two signalling molecules that are attractive for targeted therapy are the epidermal growth factor receptor (EGFR) and the peroxisome proliferator-activated receptor gamma (PPARγ). We investigated possible crosstalk between these 2 pathways, particularly in light of the recent evidence implicating PPARγ for anticancer therapy. PRINCIPAL FINDINGS: As evaluated by MTT assays, gefitinib (EGFR inhibitor) and DIM-C (PPARγ agonist) inhibited growth of 9 bladder cancer cell lines in a dose-dependent manner but with variable sensitivity. In addition, combination of gefitinib and DIM-C demonstrated maximal inhibition of cell proliferation compared to each drug alone. These findings were confirmed in vivo, where combination therapy maximally inhibited tumor growth in contrast to each treatment alone when compared to control (p<0.04). Induction of PPARγ expression along with nuclear accumulation was observed in response to increasing concentrations of gefitinib via activation of the transcription factor CCAT/enhancer-binding protein-β (CEBP-β). In these cell lines, DIM-C significantly sensitized bladder cancer cell lines that were resistant to EGFR inhibition in a schedule-specific manner. CONCLUSION: These results suggest that PPARγ agonist DIM-C can be an excellent alternative to bladder tumors resistant to EGFR inhibition and combination efficacy might be achieved in a schedule-specific manner.
No takes yet. Share an insight, caveat, or question.
Mansure et al. (2013) studied Bladder Cancer (n=40). Gefitinib and DIM-C combination vs. Placebo or each drug alone was evaluated on Tumor growth (weight) (p=<0.04). The combination of the EGFR inhibitor gefitinib and the PPAR gamma agonist DIM-C maximally inhibited bladder tumor growth in vivo compared to each treatment alone or control (p<0.04).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: