TRIPLETE is a phase III trial where 435 pts with RAS/BRAF wt – per local assessment – mCRC were randomized to receive first-line FOLFOX/ panitumumab (pan) or mFOLFOXIRI/pan... In contrast to previous data, negative hyperselection both through tissue and plasma analysis failed to demonstrate a prognostic role among pMMR RAS/BRAF wt mCRC pts treated with first-line chemotherapy plus pan. The confounding effect of the associated chemotherapy is a potential explanation for this finding. Tissue and plasma analyses at baseline failed to provide fully concordant results.

The kidneys from rats co-treated with lycopene (10 mg) + 5-FU did not show the degenerative changes in the glomerular tufts and tubules observed for the rats treated with 5-FU alone. In conclusion, LYC is a promising therapeutic strategy for attenuating 5-FU-induced nephrotoxicity through the restoration of antioxidant activities and inhibition of inflammatory responses by modulating PPAR-γ, Nrf2/HO-1, and NF-κB/TNF-α/IL-6, signals.

This study will determine the prevalence of DPYD gene variant status in Australia and its impact on FP-induced toxicity among Australians with cancer. Feasibility and cost-effectiveness for Australian health care system will be estimated to support national roll-out of prospective DPYD genotyping prior to FP administration. Additionally, feasibility will be confirmed with the intention of including UGT1A1 in future pharmacogenomic panels to aid chemotherapy prescribing.

In Type A MSI+ tumours, the patient response to fluoropyrimidine and oxaliplatin was significantly poor (Fisher's exact test, p = 0.021)...Type A MSI was an independent predictor of patient prognosis in this pilot cohort (Cox regression analysis, p = 0.003). Thus, more subtle Type A MSI better predicts fluoropyrimidine insensitivity in colorectal cancer patients, which may shed light on a hitherto overlooked connection between the MSI phenotypes and drug resistance in human cancer.

Grade based on Ki67 index and immune environment change in PanNET patients responding well to CapTem. Patients with downgraded had longer mPFS compared to those with upgraded. It is necessary to reassess the Ki67 index after CapTem treatment, even in patients responding well to CapTem.

Compound 3c induced apoptosis, as evidenced by PARP cleavage and downregulation of p-Bcl-2 and Bcl-2, and demonstrated synergistic effects in combination with the chemotherapeutic agent 5-fluorouracil. Compound 3c also showed selectivity towards hormone-dependent breast cancer cells, likely targeting ERα - a key driver in this cancer subtype. In summary, we report the development of a first-in-class antiestrogenic isocryptolepine with notable pro-apoptotic efficacy.

ERCC1 mRNA is an independent prognostic factor and predictive marker that can be used to guide the addition of docetaxel. The SNPs of ERCC1 and GSTP1 could be also prognostic or predictive factors.

Gastric cancer patients with age <60 years, TNM stage of Ⅰ ∼ Ⅱ, lymph node metastasis N0 ∼ N1, high expression of FOXP1, GGT <387.2, and combined with drug chemotherapy had higher survival rate. Capecitabine effectively enhanced the sensitivity of intermediate and advanced gastric cancer to oxaliplatin, improved the therapeutic effect, reduced the proportion of patients with low FOXP1 expression rate and serum GGT level, decreased the recurrence rate and ameliorated the prognosis of patients.

The CRC-PDX model established in this study can maintain the biological characteristics of primary tumors and can be used as a reference model for the individualized treatment of CRC patients. The degree of malignancy of the primary tumor is the primary factor affecting the tumorigenesis rate of the PDX model.

The patient was treated with a chemotherapy regimen of pemetrexed and carboplatin. Mesothelioma with predominantly intrapulmonary growth is extremely rare and poses a diagnostic pitfall. For this entity, subtle morphological features, selection of immunohistochemical markers, and electron microscopy are of great significance for definite diagnosis.

Herein, we report extended follow-up data from the INTEGA trial (NCT03409848), which investigated the efficacy of the anti-PD-1 nivolumab, trastuzumab, and FOLFOX chemotherapy (FOLFOX arm) in comparison to a chemotherapy-free regimen involving nivolumab, trastuzumab, and the anti-CTLA-4 ipilimumab (Ipi arm) in the first-line setting for advanced disease...Furthermore, a low NLR characterized patients benefiting from immune- and targeted therapy without the need for additional chemotherapy. This data suggests that patient selection based on inflammatory stress-driven immune changes could help to customize first-line treatment in patients with advanced HER2-positive EGA to potentially improve long-term survival.

The randomized phase III POST trial aimed to compare the efficacies of two adjuvant S-1-based doublet chemotherapies: S-1 plus cisplatin (SP) and S-1 plus docetaxel (DS)...The nProfiler1 assay offers valuable insights into the prognosis and efficacy of adjuvant chemotherapy based on fluorouracil plus platinum doublet regimens but not docetaxel-containing regimens. Further validation with larger patient cohorts and different regimens is warranted.

Moreover, computational ADMET analyses of these compounds demonstrated compliance with Lipinski's criteria, indicating favorable physicochemical properties. Additionally, molecular dynamics (MD) simulations revealed stable complexes of AUPF01 with EGFR, CDK2, ERalfa, BAX1, BCL2, and P53, as evidenced by (RMSD) values, RMSF values, and (SASA) values for the respective complexes.

In external validation, XGBoost model achieved an accuracy of 0.79. An online prognostic tool based on XGBoost was developed, integrating metabolism-related SNPs and inflammatory markers, enhancing CRC treatment precision and supporting tailored chemotherapy.

High LINC01764 expression correlates with metastasis, a poor response to FOLFOX/XELOX chemotherapy, and a poor prognosis in CRC...LINC01764 induced 5-FU chemoresistance by upregulating the c-MYC, glucose, and glutamine metabolism pathways, which downregulated UPP1, crucial for activating 5-FU. Conclusively, LINC01764 promotes CRC progression and 5-FU resistance through hnRNPK-mediated-c-MYC IRES-dependent translational regulation, which suggests its potential as a predictor of CRC chemotherapy response and prognosis.

P=N/A, N=30, Recruiting, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

P=N/A, N=50, Not yet recruiting, St Vincent's University Hospital, Ireland

P1/2, N=34, Completed, The First Hospital of Jilin University | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Mar 2024

P=N/A, N=20, Not yet recruiting, Affiliated Hospital OF Jiangnan University; Affiliated Hospital OF Jiangnan University

P=N/A, N=60, Not yet recruiting, Qilu Hospital of Shandong University; Qilu Hospital of Shandong University

P2, N=60, Recruiting, Tumor Hospital Affiliated to Guizhou Medical University; Tumor Hospital Affiliated to Guizhou Medical University

P2, N=400, Recruiting, Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

P2, N=30, Not yet recruiting, Fujian Medical University Affiliated Union Hospital; Fujian Medical University Affiliated Union Hospital

P2, N=20, Recruiting, Jiangsu Province Hospital; Jiangsu Province Hospital

P1, N=30, Recruiting, Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

Upregulated LINC02323 expression in gastric cancer is associated with malignant progression, adverse prognosis, and chemotherapy resistance. Silencing LINC02323 could enhance the sensitivity of gastric cancer cells to 5-FU by negatively modulating miR-139-3p expression.

Drug sensitivity analysis showed significantly higher IC50 values for 5-fluorouracil, gemcitabine, and sorafenib in patients with low MRTO4 expression than in those with high MRTO4 expression. MRTO4 acts as an independent prognostic and immunological biomarker and is correlated with clinical stage, tumor grade, and drug sensitivity in HCC. It may serve as a putative therapeutic target and potential biomarker for prognosis of HCC.

Rg3 enhances the anticancer effects of 5-FU in CRC cells that are sensitive and resistant to 5-FU, and its mechanism of action may be related to the inhibition of Hedgehog pathway activation.

5-fluorouracil (5-FU) is a preferred chemotherapeutic agent for the treatment of colon cancer...In an effort to mimic the development of colon cancer, we established an azomethane oxide (AOM)/ dextran sodium sulfate (DSS) mouse model, showing that FLCWK bolstered the inhibitory effects of 5-FU, impeding the progression of colon cancer. In summation, our findings point towards the potential of FLCWK in the treatment of colon cancer, particularly in strengthening the therapeutic efficacy of 5-FU in the prevention and control of the disease.

In the first-line treatment of HER2-positive advanced gastric cancer, inetetamab and trastuzumab showed comparable efficacy. The inetetamab group showed superior PFS, and both groups had good safety.

In conclusion, the TF KLF9 inhibits the aerobic glycolysis level of breast cancer cells by up-regulating PTEN expression, thereby reducing their resistance to 5-FU. The discovery of this mechanism provides a new theoretical basis for the treatment of breast cancer.

P3, N=1979, Recruiting, Henan Cancer Hospital | Trial primary completion date: Sep 2024 --> Sep 2025

Following this, protein kinase C delta was predicted as a possible molecular target of ATBC. These findings propose ATBC as a therapeutic agent for managing the cutaneous side effects associated with 5-FU treatment.

Results suggest that aflibercept plus FOLFIRI, after failure of a prior oxaliplatin-based regimen, allows R0/R1 resection of CLM in almost 20 % of patients with a major pathological response in most cases and a median OS prolonged by more than 3-fold versus non-resected patients.

We have comprehensively investigated the protein expression of TRIB3 in three gastric cancer cell lines AGS, TMK-1, and MKN-45 cells treated with the anticancer drugs, 5-fluorouracil, cisplatin, and docetaxel...In addition, overexpression of TRIB3 also rescued paroxetine-induced apoptosis and endoplasmic reticulum stress. Our previous and present results indicate that TRIB3 can protect gastric cancer cells against anticancer drug treatment and that downregulating TRIB3 may increase these cells' sensitivity to anticancer drugs. We thus suggest that the capability of anticancer drugs to downregulate TRIB3 can indicate tumors' potential susceptibility to these drugs.

P1, N=45, Recruiting, South Metropolitan Health Service (SMHS) | Not yet recruiting --> Recruiting

iRGD-Exo-siBRIX1 significantly suppressed the growth of colorectal cancer and enhanced the efficacy of 5-FU chemotherapy in vivo. Overall, the study uncovers that BRIX1 functions as an oncoprotein to promote rRNA synthesis and dampen p53 activity, and also implies that targeted inhibition of BRIX1 via engineered exosomes can be a potent approach for cancer therapy.

We described a case of unresectable BRCA1 L63*-mutated BCC invading the parietal bone, which was successfully treated with cisplatin and fluorouracil. Our present case suggests that comprehensive mutation analysis by gene panel testing is important in advanced BCC because genes other than those involved in the hedgehog signaling pathway can be driver genes.

This study is experimental-based and was designed using a six-group treatment method, namely normal control (KN: not treated by MNU, nanodiamond (ND), or Q); negative control (K-: treated by MNU); positive control (K+: treated by MNU and capecitabine); ND (treated by MNU and NDs); Q (treated by MNU and Q); and NDQ (treated by MNU and NDQ)...The lung tumor metastases in the NDQ group were fewer than in the K- group. NDQ increased Q's anticancer activity, suggesting that NDs have an effective drug delivery property.

TCCL relieves pathological changes in tumor tissue and chemotherapy-induced gastrointestinal injury, potentially by reducing the release of pro-inflammatory factors to repair the gastrointestinal mucosa, enhancing intestinal barrier function, and maintaining gastrointestinal microecological balance. Hence, TCCL is a very effective adjuvant to chemotherapy.

P2, N=110, Not yet recruiting, Fudan University

P3, N=545, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed