TY - JOUR
T1 - Modulation of prostaglandin-endoperoxide synthase-2 (PTGS2) mediated VEGF-signalling pathway by oral metronomic chemotherapy in locally advanced oral squamous cell Carcinoma
T2 - A brief report
AU - Kamal, Mehta Vedant
AU - Palod, Akhil
AU - Parida, Preetiparna
AU - Pai, Ananth
AU - Sharan, Krishna
AU - Belle, Vijetha Shenoy
AU - Damerla, Rama Rao
AU - Rao, Mahadev
AU - Kumar, Naveena A.N.
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.
PY - 2025/12
Y1 - 2025/12
N2 - 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).
AB - 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).
UR - https://www.scopus.com/pages/publications/105017615796
UR - https://www.scopus.com/pages/publications/105017615796#tab=citedBy
U2 - 10.1007/s00280-025-04819-z
DO - 10.1007/s00280-025-04819-z
M3 - Article
C2 - 41045400
AN - SCOPUS:105017615796
SN - 0344-5704
VL - 95
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
IS - 1
M1 - 96
ER -
