The nonsteroidal anti-inflammatory (NSAID) class of drugs, often used to treat pain and fever, includes medications like aspirin that have shown potential in CRC treatment. NSAIDs target cyclooxygenase (COX) enzymes and their associated pathways, which are relevant to tumor progression.
Aspirin, a non-selective NSAID, inhibits both COX-1 and COX-2 enzymes, while some other drugs in the NSAID class selectively target COX-2 exclusively. Because COX-2 expression appears linked to the benefits of aspirin in CRC, recent work has focused on celecoxib, a COX-2-selective inhibitor, to elucidate effects on outcomes. This research has demonstrated that celecoxib helps treat CRC cancer, but only in certain patients.
Circulating tumor DNA (ctDNA), small pieces of DNA released by tumors into the circulation, also relates to prognosis. Measuring ctDNA has proven to be cost-effective and minimally invasive to patients. While research has established some guidelines linking ctDNA to CRC prognosis, its value in treatment planning and management remains unclear.
The prominent yet not fully understood roles of celecoxib and ctDNA in CRC progression highlight the importance of ctDNA as a prognostic marker, which can help clinicians feel more confident in predicting patient outcomes and tailoring treatments. A new study, recently published in JAMA Oncology, shows that ctDNA can predict survival among patients with CRC who received adjuvant celecoxib.
The study included 940 patients with CRC who reported low-dose aspirin use before enrollment. Analysis of ctDNA showed that 81.6% of these patients were ctDNA-negative and 18.4% were ctDNA-positive. Those with ctDNA positivity had significantly poorer disease-free survival (DFS) and overall survival (OS).
However, in the cohort of patients with ctDNA positivity, celecoxib improved both DFS and OS compared with placebo. This observation did not repeat for the cohort of patients with ctDNA negativity.
This study demonstrates the prognostic value of ctDNA, showing a strong association with poor outcomes and inspiring clinicians to consider personalized strategies that could improve patient care.
Sources: NEJM, JAMA Oncol, Nat Med
