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Background <p>Locally advanced oral squamous cell carcinoma (OSCC) is associated with poor survival outcomes, particularly in resource-limited settings, where treatment delays are prevalent. Oral metronomic chemotherapy (OMCT) utilising methotrexate and celecoxib is a potentially low-toxicity, cost-effective alternative in the neoadjuvant setting.</p> Methods <p>Thirteen patients diagnosed with stage 3 or 4 resectable OSCC were enrolled in this study. Each participant received one month of OMCT prior to surgical intervention and continued OMCT as maintenance therapy following treatment. The expression levels of <i>PTGS2</i>,<i> VEGFA</i>,<i> VEGFB</i>,<i> KDR</i>,<i> CXCR1</i>, and <i>CXCR2</i> were analysed both before and after OMCT administration. Additionally, organ function and patient survival were evaluated to determine the efficacy and toxicity of treatment.</p> Results <p><i>PTGS2</i>,<i> VEGFA</i>,<i> VEGFB</i>, and <i>KDR</i> were significantly upregulated in the tumour tissues at baseline. Post-OMCT, <i>VEGFA</i>, <i>VEGFB</i>, and <i>KDR</i> were significantly downregulated, whereas <i>PTGS2</i> expression increased. No significant changes were observed in <i>CXCR1</i> and <i>CXCR2</i> expression. Liver, renal, and thyroid functions remained within normal limits. No adverse events were reported. The median overall survival was 22.1 months, and the median disease-free survival was 20 months. Upregulation of <i>PTGS2</i>, <i>VEGFA</i>, and <i>VEGFB</i> was correlated with improved outcomes.</p> Conclusion <p>OMCT has the potential to manage disease progression in patients with OSCC awaiting surgical intervention. It is characterised by low toxicity and may exert anti-angiogenic effects through modulation of the VEGF pathway. Further large-scale trials are necessary to substantiate these findings and to establish optimal treatment strategies.</p> Trial registration <p>The study was also registered in the Clinical Trials Registry of India (registration number: CTRI/2021/01/030256).</p>

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Modulation of prostaglandin-endoperoxide synthase-2 (PTGS2) mediated VEGF-signalling pathway by oral metronomic chemotherapy in locally advanced oral squamous cell Carcinoma: A brief report

  • 期刊论文

  • 发表日期：

    2025年10月4日

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  • Mehta Vedant Kamal,
  • Akhil Palod,
  • Preetiparna Parida,
  • Ananth Pai,
  • Krishna Sharan,
  • Vijetha Shenoy Belle,
  • Rama Rao Damerla,
  • Mahadev Rao,
  • Naveena A. N. Kumar

摘要

Background

Locally advanced oral squamous cell carcinoma (OSCC) is associated with poor survival outcomes, particularly in resource-limited settings, where treatment delays are prevalent. Oral metronomic chemotherapy (OMCT) utilising methotrexate and celecoxib is a potentially low-toxicity, cost-effective alternative in the neoadjuvant setting.

Methods

Thirteen patients diagnosed with stage 3 or 4 resectable OSCC were enrolled in this study. Each participant received one month of OMCT prior to surgical intervention and continued OMCT as maintenance therapy following treatment. The expression levels of PTGS2, VEGFA, VEGFB, KDR, CXCR1, and CXCR2 were analysed both before and after OMCT administration. Additionally, organ function and patient survival were evaluated to determine the efficacy and toxicity of treatment.

Results

PTGS2, VEGFA, VEGFB, and KDR were significantly upregulated in the tumour tissues at baseline. Post-OMCT, VEGFA, VEGFB, and KDR were significantly downregulated, whereas PTGS2 expression increased. No significant changes were observed in CXCR1 and CXCR2 expression. Liver, renal, and thyroid functions remained within normal limits. No adverse events were reported. The median overall survival was 22.1 months, and the median disease-free survival was 20 months. Upregulation of PTGS2, VEGFA, and VEGFB was correlated with improved outcomes.

Conclusion

OMCT has the potential to manage disease progression in patients with OSCC awaiting surgical intervention. It is characterised by low toxicity and may exert anti-angiogenic effects through modulation of the VEGF pathway. Further large-scale trials are necessary to substantiate these findings and to establish optimal treatment strategies.

Trial registration

The study was also registered in the Clinical Trials Registry of India (registration number: CTRI/2021/01/030256).