Adjuvant aspirin and Cyclooxygenase-2 inhibitors in resected, PIK3CA-mutated colorectal cancer: A systematic review and meta-analysis of randomized controlled trials

Review

作者: Dabbous de Liz, Caio ; Abrahão Reis, Pedro C ; Blanchard-Cavagis, Ellen R ; Carneiro Brito, Heloísa ; Diniz, Isabela C ; Visani, Filipe Luis Vasconcelos

BACKGROUND:

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are widely available and inexpensive agents with proposed antitumor activity, particularly in tumors harboring PIK3CA mutations. This meta-analysis of randomized controlled trials (RCTs) evaluated whether adjuvant NSAID therapy improves outcomes in patients with resected PIK3CA-mutated colorectal cancer (CRC).

METHODS:

PubMed, Embase, and the Cochrane Library were systematically searched for RCTs assessing NSAID use following curative-intent resection of CRC in patients with confirmed PIK3CA mutations. Pooled hazard ratios (HRs) with corresponding 95 % confidence intervals (CIs) were calculated for disease-free survival (DFS) and overall survival (OS) using both fixed and random-effects models. Sensitivity analyses excluded participants with low-dose aspirin exposure concomitant with cyclooxygenase-2 (COX-2) inhibitors.

RESULTS:

Among 477 records screened, four RCTs met eligibility criteria, comprising 426 patients assigned to NSAIDs (aspirin or COX-2 inhibitors) and 363 receiving placebo. Adjuvant NSAID therapy improves DFS (HR 0.65; 95 % CI, 0.46-0.90). In sensitivity analyses excluding concomitant aspirin exposure, a similar magnitude of effect was observed (HR 0.57; 95 % CI, 0.39-0.83). The pooled OS analysis was not statistically significant (HR 0.78; 95 % CI, 0.39-1.57). Exclusion of low-dose aspirin users was associated with lower mortality risk (HR 0.54; 95 % CI, 0.30-0.99), although these findings should be interpreted cautiously.

CONCLUSION:

Adjuvant NSAID therapy is associated with improved DFS in patients with PIK3CA-mutated CRC. OS benefit remains uncertain, and findings from sensitivity analyses are exploratory. These findings support consideration of NSAIDs as a biomarker-informed adjuvant strategy in selected patients while underscoring the need for confirmatory evidence from ongoing randomized trials.

2026-02-01·DIGESTIVE AND LIVER DISEASE

Comparing the efficacy and safety of medications to prevent nonsteroidal anti-inflammatory drug-induced ulcers in high-risk patients: A network meta-analysis

Review

作者: Gong, Chenxi ; Fang, Qingying ; Pei, Dongmei ; Zhou, Liwei ; Huang, Xu

The optimal strategy for preventing nonsteroidal anti-inflammatory drug-induced peptic ulcers in patients with prior peptic ulcers remains uncertain. We performed a systematic review and network meta-analysis of 22 randomized controlled trials (7,768 patients) on nonsteroidal anti-inflammatory drug users with a documented ulcer history to compare the efficacy and safety of medications for the prevention of these ulcers. The eligible interventions included proton pump inhibitors, potassium-competitive acid blockers, cyclooxygenase-2 inhibitors, prostaglandin analogs, histamine-2 receptor antagonists, and gastric mucosal protective agents. The primary outcomes were ulcer recurrence and bleeding. The safety outcomes included treatment-emergent adverse events and discontinuation owing to adverse events. Random-effects network models estimated the relative and absolute risks, numbers needed to treat, and rankings. Compared with placebo, cyclooxygenase-2 inhibitor plus proton pump inhibitor, potassium-competitive acid blocker, cyclooxygenase-2 inhibitor alone, and proton pump inhibitor monotherapy markedly reduced ulcer recurrence (numbers needed to treat = 5-6). Similar patterns were observed for bleeding prevention. Prostaglandin analogs increased adverse events and discontinuations. Proton pump inhibitor monotherapy remains the most evidence-based first-line strategy for these patients. Cyclooxygenase-2 inhibitor plus proton pump inhibitors or potassium-competitive acid blockers may provide additional benefits in very high-risk patients, but safety and cost considerations warrant caution.

2026-01-01·FITOTERAPIA

Targeted isolation of new di/trinormonoterpenoid glucosides as cyclooxygenase-2 inhibitors from Periplocae Cortex using molecular networking

Article

作者: Tang, Xi-Yang ; Li, Zi-Ting ; Wang, Hang-Hang ; Dai, Yi ; Ou, Zong-Jin ; Fan, Cai-Lian ; Chen, Wei-Wu ; Shu, Zhi-Heng

In this study, two tri- and three dinormonoterpenoid glucosides, named xiangjiapiosides A-E (1-5), were extracted and purified from the ethanol extract of Periplocae Cortex (PC) by employing a combined approach of HP-20 resin, silica gel, ODS, and semi-preparative high performance liquid chromatography (HPLC) under the guidance of molecular networking based on tandem mass spectrometry (MS/MS). The structural determination of these compounds was achieved by conducting detailed spectroscopic analyses involving nuclear magnetic resonance spectroscopy (NMR) and circular dichroism (CD). Anti-inflammatory evaluation revealed that compounds 1, 2, 4, and 5 exerted a significant suppressive effect on the generation of nitric oxide (NO), tumour necrosis factor-alpha (TNF-α), and Interleukin-6 (IL-6), and down-regulated the expression of cyclooxygenase-2 (COX-2). The COX-2 enzyme inhibitory activities of these compounds were notable, and the corresponding IC₅₀ values were 18.82, 41.54, 26.97, and 13.41 μM. Docking analysis results demonstrated that compounds 1, 2, 4, and 5 had the capacity to occupy the catalytic domain of COX-2 enzymes, exhibiting analogous binding conformations to those observed with the selective COX-2 inhibitor celecoxib. All these findings implied that these di/trinormonoterpenoid glucosides derived from PC possess promising characteristics for development as novel COX-2-targeted therapeutic agents.

项与 BIRL-790 相关的新闻（医药）

2024-04-30

·FierceBiotech

Sweet Harmony: Neuro biotech buys Epygenix and its epilepsy meds for $35M upfront

Harmony's latest deal comes as revenue jumped 30% in the first quarter of 2024 compared to the same period a year ago. Harmony Biosciences is adding a suite of epilepsy assets to its pipeline, buying Epygenix for $35 million upfront with more than $600 million in biobucks on the table. The relatively small M&A deal announced Tuesday has large potential, with the purchase adding a third late-stage candidate to Harmony’s pipeline. Front and center is EPX-100, currently in a phase 3 study to treat Dravet syndrome in both adults and children. Epygenix is about to launch a second phase 3 study in children with Lennox-Gastaut syndrome, a rare epilepsy condition. “The acquisition of Epygenix gives us three distinct CNS franchises in late-stage development, each with a potential US peak sales opportunity of $1B - $2B," said Harmony President and CEO Jeffrey Dayno, M.D. Analysts at Mizuho, commenting on both the deal and the company’s broader progress, could hardly contain their excitement—at least in investor speak. “We come away very pleased with [Harmony’s] updates this morning,” they wrote. The company’s shares were up 13% shortly after the markets opened Tuesday, from $29.25 to $33.04, indicative of wider investor positivity beyond just Mizuho’s enthusiastic note. It’s Harmony’s second BD play in less than a month after the biotech scooped up an orexin-2 inhibitor from Bioproject to test as a narcolepsy treatment in early April. Takeda and Jazz Pharmaceuticals have each tried to tackle the target, though side effects have made the road a bit rockier. Harmony paid Bioproject $25.5 million to take hold of TPM-1116, with nearly $370 million in milestone payments up for grabs. That purchase added depth to Harmony’s blossoming sleep disorder franchise, led by approved narcolepsy med Wakix. The drug raked in $154.6 million in revenue in the first quarter, a 30% increase from the same period a year ago. Harmony is looking to pad the stats through additional indications, with plans to submit a supplemental new drug application to the FDA in the second half of the year for Wakix to treat idiopathic hypersomnia, a condition marked by excessive sleepiness. The biotech is also working on a new formulation of the drug with a PDUFA date expected in 2026.