A novel drug combination strategy that redesigns the pharmacological management of oral cancer.

Rajdeep Chakraborty*, Charbel Darido, Honghua Hu, Karen Vickery, Shoba Ranganathan

*Corresponding author for this work

Research output: Contribution to journalMeeting abstract


Background: Biofilm formation is a continuous process in oral cancer patients, despite proper extirpation/elimination of a bacterial plaque via a surgical procedure or antibiotic treatment. Also, elimination of a bacterial plaque does not necessarily remove extant bacterial antigen-stimulated oral cancer cells. Therefore, combination drug treatment may be an appropriate approach to elucidate the confounding effects of bacterial antigens on anti-cancer drugs. Methods: Our drug combination strategy addressed both Gram-positive (Lipoteichoic acid [LTA]) and Gram-negative (Lipopolysaccharide [LPS]) bacterial antigens, to determine the effect of anti-cancer drugs on LPS/LTA/LPS+LTA-stimulated preclinical oral cancer models (SCC4, SCC9, SCC25, and Cal 27). The drug combination strategy was designed in six phases of treatment. In phase 1, plated cells were treated with different combinations of bacterial antigens in combination with anti-cancer drugs. In the phases 2 and 3, inhibitory drugs were introduced in the presence of bacterial antigens after 24 hours and 72 hours of bacterial antigen stimulation. In phases 4 and 5, inhibitory drugs were added after 24 hours and 72 hours of bacterial antigen stimulation. In phase 6, inhibitory drugs were applied in the absence of, and without stimulation with, bacterial antigens. Metabolic assays, reverse transcription quantitative PCR, Western blot, Proteome Profiler, apoptotic and ELISA assays were performed to validate the novel drug combination strategy. Results: Anti-cancer drug treatment on preclinical oral cancer models resulted in 43.6% ± 3.3% of precancerous models being apoptotic. To mimic pre-existing unhygenic conditions in oral cancer patients, prior stimulation of preclinical model with LPS+LTA 72 hours before drug treatment, reduced apoptosis to 32.2% ± 1.1% of cells. Apoptosis was almost annulled (2.98% ± 0.3%; p < 0.01) when drug treatment was carried out along with bacterial antigens. Treatment with drugs in the absence of bacterial antigens resulted in significantly more apoptotic cells than in presence of bacterial antigens (p < 0.0001). Metabolic and viability assay showed similar results like apoptotic assay. Conclusions: Bacterial antigens mimic the presence of Gram-negative and Gram-positive bacteria and thus severely affect the efficacy of anti-cancer drugs. The novel drug combination strategy redesigns the pharmacological management of oral squamous cell carcinoma.
Original languageEnglish
Article numbere18053
Pages (from-to)18053-18053
Number of pages1
JournalJournal of Clinical Oncology
Issue number16 Suppl.
Publication statusPublished - 2022
EventAnnual Meeting of the American Society of Clinical Oncology, ASCO 2022 - Chicago, United States
Duration: 3 Jun 20227 Jun 2022


  • Oral cancer
  • Biofilm
  • Proliferation
  • Apoptosis
  • Bacterial antigen


Dive into the research topics of 'A novel drug combination strategy that redesigns the pharmacological management of oral cancer.'. Together they form a unique fingerprint.

Cite this