Pancreatic Cancer Protein Offers New Path to Better Treatment
A Swedish-Finnish study found that one-quarter of pancreatic cancer patients have tumors expressing a protein called CLDN18.2, which is already being targeted by new drugs. Patients with this protein lived significantly longer after surgery, suggesting screening for it could help oncologists select better treatment strategies and improve survival rates.
Originaltitel: Prognostic Value of Intratumoral Expression of Claudin 18.2 in Resected Pancreatic Cancer.
CLDN18.2-positiva tumörer utgör ett potentialt terapeutiskt målområde för cirka en fjärdedel av pankreascancerpatienter. Svenska och finska forskare analyserade 599 primära tumörer och 197 lymfkörtelmetastaser från patienter med resektabel pankreaskörtelcancer och identifierade CLDN18.2-positivitet i 23 procent av primärtumörerna och 17,8 procent av metastaserna. Patienter med CLDN18.2-positiva tumörer uppvisade längre mediaöverliv (27,7 jämfört med 21,1 månader) och CLDN18.2-positivitet fungerade som oberoende prognostisk markör. Forskningsteamet från Umeå universitet och helsingforsuniversitetet bekräftar att CLDN18.2 kan användas både som prognostisk biomarkör och terapeutisk målpunkt. För investerare och biopharmabolag är resultaten relevanta då pågående kliniska försök utvärderar CLDN18.2-riktade terapier vid metastatisk pankreaskörtelcancer — denna studie validerar målpunktens kliniska värde och patientpopulationens storlek.
BACKGROUND: Targeting Claudin-18 isoform 2 (CLDN18.2) improves survival in CLDN18.2 positive advanced gastric cancer and similar trials on metastatic pancreatic ductal adenocarcinoma (PDAC) are ongoing. Here, we aimed to assess the prevalence of CLDN18.2 positivity in resected PDAC including its association with overall survival (OS). METHODS: Immunohistochemical analysis on paraffin-embedded primary tumors and lymph node metastases was performed from patients who underwent curative-intent PDAC resection at four centers in Sweden and Finland. In addition, survival outcomes were assessed. RESULTS: In total, 599 primary tumors and 197 lymph nodes were analyzed. CLDN18.2 positivity was observed in 138 of 599 of primary tumors (23%) and 35 of 197 metastatic lymph nodes (17.8%). CLDN18.2 positivity in primary tumors was associated with higher tumor grade (p = 0.016). Median OS was longer in patients with CLDN18.2-positive tumors (27.7 vs. 21.1 months). Adjusted analysis identified CLDN18.2 positivity as an independent prognostic variable for OS (hazard ratio 0.79; 95% confidence interval 0.64-0.98). CONCLUSIONS: CLDN18.2 is expressed in 23% of primary PDAC tumours, indicating its potential to be used as a therapeutic target in a significant proportion of PDAC patients, and its expression is associated with improved OS in resected PDAC, supporting its role as a prognostic marker.